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Sample records for acute dengue infections

  1. Acute neuromuscular weakness associated with dengue infection

    PubMed Central

    Hira, Harmanjit Singh; Kaur, Amandeep; Shukla, Anuj

    2012-01-01

    Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK) were tested. In addition, two patients underwent nerve conduction velocity (NCV) test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2nd to 4th day of illness in 11 of 12 patients. In one patient, it developed on 10th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients. PMID:22346188

  2. Dengue-induced Acute Kidney Injury (DAKI): A Neglected and Fatal Complication of Dengue Viral Infection--A Systematic Review.

    PubMed

    Mallhi, Tauqeer Hussain; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Yusra Habib; Hamzah, Azhar Amir; Jummaat, Fauziah; Khan, Amer Hayat

    2015-11-01

    Dengue Viral Infection (DVI) imperils an estimated 2.5 billion people living in tropical and subtropical regions. World Health Organization (2011) guidelines also classified dengue as 'Expanded Dengue Syndrome' to incorporate wide spectrum of unusual manifestations of dengue infection affecting various organ systems - including liver, kidney, heart and brain. Renal involvements are least appreciated area of dengue infection, therefore, we systematically reviewed studies describing renal disorders in dengue infection, with emphasis on Acute Kidney Injury (AKI). The purpose of current review is to underscore clinicians’attention to this neglected intricacy of DVI. It suggests that dengue induced renal involvements vary from glomerulonephritis, nephrotic range proteinuria and AKI. We observed great disparity in incidence of AKI among dengue patients, based upon criteria used to define AKI. AKI among dengue patients was found to be associated with significant morbidity, mortality and longer hospitalization, adding financial burden to patients and healthcare system. Additionally, we identified several predictors of AKI in dengue patients including old age, obesity, severe dengue infection and concurrent bacterial or viral infection. Direct viral injury and deposition of antigen-antibody complex in glomerulus were found to be possible causes of renal disorders in dengue infection. Prior knowledge of clinico-laboratory characteristics and risk factors with early detection of AKI by using appropriate criteria would not only reduce morbidity and mortality but also decrease burden to patients and healthcare system. PMID:26577971

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

    PubMed Central

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

    2016-01-01

    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. PMID:27240351

  4. 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

    2016-01-01

    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. PMID:27240351

  5. A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infection

    PubMed Central

    Rossi, Fernanda C.; Angerami, Rodrigo N.; de Paula, Erich V.; Orsi, Fernanda L.; Shang, Dezhi; del Guercio, Vânia M.; Resende, Mariângela R.; Annichino-Bizzacchi, Joyce M.; da Silva, Luiz J.; Zheng, X. Long; Castro, Vagner

    2011-01-01

    BACKGROUND Dengue is a mosquito-borne viral disease with an increasing incidence worldwide. Thrombocytopenia is a common finding in dengue virus (DV) infection; however, the underlying mechanisms remain unknown. CASE REPORT Here we provide the first evidence of a case of antibody formation against ADAMTS13 (ADAMTS13 inhibitor) in the course of a severe acute DV infection resulting in thrombotic microangiopathy (TMA). The patient presented with classical dengue symptoms (positive epidemiology, high fever, myalgia, predominantly in the lower limbs and lumbar region for 1 week) and, after 11 days of initial symptoms, developed TMA. Clinical and laboratorial investigation of dengue and TMA was performed. RESULTS The patient presented with ADAMTS13 inhibitor (IgG) during the acute phase of the disease, without anti-platelet antibodies detectable. Dengue infection had laboratorial confirmation. There were excellent clinical and laboratory responses to 11 serial plasma exchanges. Anti-ADAMTS13 inhibitor disappeared after remission of TMA and dengue resolution. No recurrence of TMA symptoms was observed after 2-year follow-up. CONCLUSIONS Although the real incidence of dengue-related TMA is unknown, this case provides the basis for future epidemiologic studies on acquired ADAMTS13 deficiency in DV infection. The prompt clinical recognition of this complication and early installment of specific therapy with plasma exchange are likely to improve the outcome of severe cases of dengue. PMID:19788513

  6. Immunoglobulin G antibody response in children and adults with acute dengue 3 infection.

    PubMed

    Vazquez, Susana; Acosta, Nadia; Ruiz, Didye; Calzada, Naifi; Alvarez, Angel M; Guzman, Maria G

    2009-07-01

    Using a serological test, different criteria have been established for classifying a case as primary or secondary dengue virus infection. Considering the dengue epidemiological situation in Cuba, IgG antibody response to dengue virus infection in serum samples from children and adults with a dengue 3 infection, in Havana city during the 2001-2002 epidemic was evaluated. Samples were collected on days 5-7 of fever onset and tested by an ELISA inhibition. A total of 713 serum samples positive for IgM antibody, 93 from children and 620 from adult patients were studied. Serum samples collected from healthy blood donors and patients not infected with dengue were included as controls. An IgG primary infection pattern was observed in sera collected from children, with titers of < or =20 in the 89.3% of the patients, while both, a primary and secondary patterns were observed in sera collected from adult patients with titers of < or =20 (13.4%) and > or =1280 (83.9%), respectively. These results permitted the definition of a primary or secondary case of dengue virus infection in serum samples collected during the acute phase of dengue virus infection.

  7. EVALUATION OF A COMMERCIAL RAPID TEST KIT FOR DETECTION OF ACUTE DENGUE INFECTION.

    PubMed

    Krishnananthasivam, Shivankari; Fernando, Anira N; Tippalagama, Rashmi; Tennekoon, Rashika; De Man, Jeroen; Seneviratne, Dammika; Premawansa, Sunil; Premawansa, Gayani; De Silva, Aruna Dharshan

    2015-07-01

    Early diagnosis is important for clinical management of dengue disease. While classic laboratory tests are often tedious and time consuming, point of care devices offer a rapid, cost-effective and user-friendly alternative provided their accuracy is acceptable. This study evaluated the sensitivity, specificity and efficiency of SD BIOLINE Dengue Duo® rapid NS1, IgM and IgG test kit for diagnosis of acute dengue virus infection. Standard laboratory diagnostics, RT-PCR, IgM and IgG capture ELISAs were carried out on 143 suspected dengue patient samples obtained from a Sri Lankan population. Using the results of these standard laboratory tests as reference, the sensitivity and specificity of the SD Dengue Duo® NS1 test was 57% and 87%, respectively, and those of the IgM test was 50% and 84%, respectively. The combined sensitivity and specificity of the SD Dengue Duo® NS1/ IgM test was 72% and 80%, respectively. The SD Dengue Duo® NS1 test detected NS1 for up to 9 days from onset of fever. Primary and secondary dengue cases were classified according to the IgG test, of which the kit identified 88% and 26% of primary and of secondary infection, respectively. Although the SD Dengue Duo® kit was not as accurate as the standard tests, it still can serve the useful reference for initial screening of suspected dengue cases, especially in poor resource hospital settings and aid in clinical disease management of dengue infection. PMID:26867379

  8. 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

  9. Neurological complication of dengue infection.

    PubMed

    Murthy, J M K

    2010-01-01

    Dengue infection is endemic in more than 100 countries, mostly in the developing world. Recent observations indicate that the clinical profile of dengue is changing, and that neurological manifestations are being reported more frequently. The exact incidence of various neurological complications is uncertain. The pathogenesis of neurological manifestations is multiple and includes: neurotrophic effect of the dengue virus, related to the systemic effects of dengue infection, and immune mediated. In countries endemic to dengue, it will be prudent to investigate for dengue infection in patients with fever and acute neurological manifestations. There is need for understanding of the pathogenesis of various neurological manifestations.

  10. Increased frequencies of CD4+CD25high regulatory T cells in acute dengue infection

    PubMed Central

    Lühn, Kerstin; Simmons, Cameron P.; Moran, Edward; Dung, Nguyen Thi Phuong; Chau, Tran Nguyen Bich; Quyen, Nguyen Than Ha; Thao, Le Thi Thu; Van Ngoc, Tran; Dung, Nguyen Minh; Wills, Bridget; Farrar, Jeremy; McMichael, Andrew J.; Dong, Tao; Rowland-Jones, Sarah

    2007-01-01

    Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4+CD25highFoxP3+ T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P < 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease. PMID:17452519

  11. A prospective case-control study to investigate retinal microvascular changes in acute dengue infection.

    PubMed

    Tan, Petrina; Lye, David C; Yeo, Tun Kuan; Cheung, Carol Y; Thein, Tun-Linn; Wong, Joshua G; Agrawal, Rupesh; Li, Ling-Jun; Wong, Tien-Yin; Gan, Victor C; Leo, Yee-Sin; Teoh, Stephen C

    2015-01-01

    Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 μm vs 144.3 μm, p < 0.001; 227.7 μm vs 212.8 μm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x10(4)], p < 0.001; 0.849 vs 0.658 [x10(4)], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system.

  12. Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans.

    PubMed

    Wrammert, Jens; Onlamoon, Nattawat; Akondy, Rama S; Perng, Guey C; Polsrila, Korakot; Chandele, Anmol; Kwissa, Marcin; Pulendran, Bali; Wilson, Patrick C; Wittawatmongkol, Orasri; Yoksan, Sutee; Angkasekwinai, Nasikarn; Pattanapanyasat, Kovit; Chokephaibulkit, Kulkanya; Ahmed, Rafi

    2012-03-01

    Humoral immune responses are thought to play a major role in dengue virus-induced immunopathology; however, little is known about the plasmablasts producing these antibodies during an ongoing infection. Herein we present an analysis of plasmablast responses in patients with acute dengue virus infection. We found very potent plasmablast responses that often increased more than 1,000-fold over the baseline levels in healthy volunteers. In many patients, these responses made up as much 30% of the peripheral lymphocyte population. These responses were largely dengue virus specific and almost entirely made up of IgG-secreting cells, and plasmablasts reached very high numbers at a time after fever onset that generally coincided with the window where the most serious dengue virus-induced pathology is observed. The presence of these large, rapid, and virus-specific plasmablast responses raises the question as to whether these cells might have a role in dengue immunopathology during the ongoing infection. These findings clearly illustrate the need for a detailed understanding of the repertoire and specificity of the antibodies that these plasmablasts produce.

  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. Comparison of Seven Commercial Antigen and Antibody Enzyme-Linked Immunosorbent Assays for Detection of Acute Dengue Infection

    PubMed Central

    Jarman, Richard G.; Gibbons, Robert V.; Tanganuchitcharnchai, Ampai; Mammen, Mammen P.; Nisalak, Ananda; Kalayanarooj, Siripen; Bailey, Mark S.; Premaratna, Ranjan; de Silva, H. Janaka; Day, Nicholas P. J.; Lalloo, David G.

    2012-01-01

    Seven commercial assays were evaluated to determine their suitability for the diagnosis of acute dengue infection: (i) the Panbio dengue virus Pan-E NS1 early enzyme-linked immunosorbent assay (ELISA), second generation (Alere, Australia); (ii) the Panbio dengue virus IgM capture ELISA (Alere, Australia); (iii) the Panbio dengue virus IgG capture ELISA (Alere, Australia); (iv) the Standard Diagnostics dengue virus NS1 antigen ELISA (Standard Diagnostics, South Korea); (v) the Standard Diagnostics dengue virus IgM ELISA (Standard Diagnostics, South Korea); (vi) the Standard Diagnostics dengue virus IgG ELISA (Standard Diagnostics, South Korea); and (vii) the Platelia NS1 antigen ELISA (Bio-Rad, France). Samples from 239 Thai patients confirmed to be dengue virus positive and 98 Sri Lankan patients negative for dengue virus infection were tested. The sensitivities and specificities of the NS1 antigen ELISAs ranged from 45 to 57% and 93 to 100% and those of the IgM antibody ELISAs ranged from 85 to 89% and 88 to 100%, respectively. Combining the NS1 antigen and IgM antibody results from the Standard Diagnostics ELISAs gave the best compromise between sensitivity and specificity (87 and 96%, respectively), as well as providing the best sensitivity for patients presenting at different times after fever onset. The Panbio IgG capture ELISA correctly classified 67% of secondary dengue infection cases. This study provides strong evidence of the value of combining dengue virus antigen- and antibody-based test results in the ELISA format for the diagnosis of acute dengue infection. PMID:22441389

  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. 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.

  17. 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

  18. 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.

  19. Dengue infection.

    PubMed

    Guzman, Maria G; Gubler, Duane J; Izquierdo, Alienys; Martinez, Eric; Halstead, Scott B

    2016-01-01

    Dengue is widespread throughout the tropics and local spatial variation in dengue virus transmission is strongly influenced by rainfall, temperature, urbanization and distribution of the principal mosquito vector Aedes aegypti. Currently, endemic dengue virus transmission is reported in the Eastern Mediterranean, American, South-East Asian, Western Pacific and African regions, whereas sporadic local transmission has been reported in Europe and the United States as the result of virus introduction to areas where Ae. aegypti and Aedes albopictus, a secondary vector, occur. The global burden of the disease is not well known, but its epidemiological patterns are alarming for both human health and the global economy. Dengue has been identified as a disease of the future owing to trends toward increased urbanization, scarce water supplies and, possibly, environmental change. According to the WHO, dengue control is technically feasible with coordinated international technical and financial support for national programmes. This Primer provides a general overview on dengue, covering epidemiology, control, disease mechanisms, diagnosis, treatment and research priorities. PMID:27534439

  20. 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

  1. Dengue viral infection.

    PubMed

    Sarin, Y K; Singh, S; Singh, T

    1998-02-01

    Dengue viral infection produces a spectrum of disease. For example, mild dengue disease is characterized by biphasic fever, myalgia, arthralgia, leukopenia, and lymphadenopathy, while dengue hemorrhagic fever is an often fatal disease characterized by hemorrhages and shock syndrome. The disease, especially in its severe form, is seen more often among children than among adults. With focus upon India, dengue's etiology, epidemiology, pathology, pathogenesis of dengue hemorrhagic fever, clinical manifestations of both the mild and severe forms of dengue viral infection, diagnosis, differential diagnosis, treatment, prevention, and prognosis are discussed.

  2. [Acute renal failure after dengue virus infection: A pediatric case report].

    PubMed

    Nicolon, C; Broustal, E

    2016-01-01

    Dengue is an emerging, rapidly expanding disease, whose clinical and biological manifestations vary. Kidney injury is not usual but can be severe, and it is most often associated with dengue hemorrhagic fever or shock. Guadeloupe, which is located in an endemic area, experienced an epidemic from 2013 to 2014. During this outbreak, a case of renal failure during dengue was observed in a 10-year-old child. No evidence of dengue hemorrhagic fever or shock syndrome was found. The clinical and biological course improved with symptomatic treatment. The association of acute renal failure with hemolytic anemia suggested a diagnosis of hemolytic uremic syndrome. However, this could not be confirmed in the absence of thrombocytopenia and cytopathologic evidence. This case illustrates the diversity of clinical presentations of dengue, and the possibility of severe renal impairment unrelated to the usual factors encountered in dengue.

  3. Outcome of Severe Dengue Viral Infection-caused Acute Liver Failure in Thai Children.

    PubMed

    Laoprasopwattana, Kamolwish; Jundee, Puthachat; Pruekprasert, Pornpimol; Geater, Alan

    2016-06-01

    To determine clinical course and outcomes of liver functions in children with dengue viral infection-caused acute liver failure (ALF), the records of patients aged <15 years attending our institution during 1989-2011 were reviewed. Of the 41 ALF patients, 2, 6 and 33 patients had dengue hemorrhagic fever grade II, III and IV, respectively. Multiorgan failure including respiratory failure, massive bleeding and acute kidney injury occurred in 80.0%, 96.0% and 84.0% of the ALF cases, respectively, with an overall fatality rate of 68.3%. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were highest on the day that the patient developed ALF. Lactate dehydrogenase levels had positive correlations with AST (r = 0.95) and ALT (r = 0.87) (all p < 0.01). The median (interquartile range) days before the AST and ALT levels returned to lower than 200 U/L after the ALF were 10.5 (8.8, 12.8) and 10.5 (7.8, 14.0) days, respectively.

  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. DENGUE VIRAL INFECTIONS

    PubMed Central

    Gurugama, Padmalal; Garg, Pankaj; Perera, Jennifer; Wijewickrama, Ananda; Seneviratne, Suranjith L

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections. PMID:20418983

  6. Dengue viral infections.

    PubMed

    Gurugama, Padmalal; Garg, Pankaj; Perera, Jennifer; Wijewickrama, Ananda; Seneviratne, Suranjith L

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  7. DENGUE INFECTION IN PREGNANCY.

    PubMed

    Khamim, Kriangsak; Khamim, Boonluck; Pengsaa, Krisana

    2015-01-01

    While dengue infection is still on the increase in adults in Thailand, it also affects pregnant women, especially pregnant teenagers. This study was designed to investigate dengue infection during pregnancy. Seven cases of dengue infection in pregnant women were admitted to Ban Pong Hospital, Ratchaburi, Thailand, between 2008 and 2012. Dengue infection presented in all pregnancy trimesters. There were two severe cases: one was dengue hemorrhagic fever in the first trimester, and the second was at a critical stage of the infection during labor. There were three cases of abortion. These three cases included one complete, one incomplete, and one threatened abortion, with rising hematocrits of 22.8%, 17.1%, and 14.7%, respectively. Two out of the three teenage pregnancies experienced complete and threatened abortions, while the third abortion case was a threatened abortion pregnancy at the critical stage of infection during intrapartum. Leukopenia was identified in six out of seven women. Low baseline hematocrit and low maximum hematocrit were laboratory findings. Clinical management involved administration of intravenous fluids and antipyretics. Favorable outcomes can be obtained through early diagnosis and supportive treatment. The morbidity profile can be more serious in teenage pregnancies. Additional studies should be conducted to establish whether low baseline hematocrit, low percentages of rising hematocrit in pregnant women with dengue infection, and abortions (with a high degree of increasing hematocrit during the critical stage of the disease) are typical clinical signs.

  8. DENGUE INFECTION IN PREGNANCY.

    PubMed

    Khamim, Kriangsak; Khamim, Boonluck; Pengsaa, Krisana

    2015-01-01

    While dengue infection is still on the increase in adults in Thailand, it also affects pregnant women, especially pregnant teenagers. This study was designed to investigate dengue infection during pregnancy. Seven cases of dengue infection in pregnant women were admitted to Ban Pong Hospital, Ratchaburi, Thailand, between 2008 and 2012. Dengue infection presented in all pregnancy trimesters. There were two severe cases: one was dengue hemorrhagic fever in the first trimester, and the second was at a critical stage of the infection during labor. There were three cases of abortion. These three cases included one complete, one incomplete, and one threatened abortion, with rising hematocrits of 22.8%, 17.1%, and 14.7%, respectively. Two out of the three teenage pregnancies experienced complete and threatened abortions, while the third abortion case was a threatened abortion pregnancy at the critical stage of infection during intrapartum. Leukopenia was identified in six out of seven women. Low baseline hematocrit and low maximum hematocrit were laboratory findings. Clinical management involved administration of intravenous fluids and antipyretics. Favorable outcomes can be obtained through early diagnosis and supportive treatment. The morbidity profile can be more serious in teenage pregnancies. Additional studies should be conducted to establish whether low baseline hematocrit, low percentages of rising hematocrit in pregnant women with dengue infection, and abortions (with a high degree of increasing hematocrit during the critical stage of the disease) are typical clinical signs. PMID:26506742

  9. Acute Febrile Illness Surveillance in a Tertiary Hospital Emergency Department: Comparison of Influenza and Dengue Virus Infections

    PubMed Central

    Lorenzi, Olga D.; Gregory, Christopher J.; Santiago, Luis Manuel; Acosta, Héctor; Galarza, Ivonne E.; Hunsperger, Elizabeth; Muñoz, Jorge; Bui, Duy M.; Oberste, M. Steven; Peñaranda, Silvia; García-Gubern, Carlos; Tomashek, Kay M.

    2013-01-01

    In 2009, an increased proportion of suspected dengue cases reported to the surveillance system in Puerto Rico were laboratory negative. As a result, enhanced acute febrile illness (AFI) surveillance was initiated in a tertiary care hospital. Patients with fever of unknown origin for 2–7 days duration were tested for Leptospira, enteroviruses, influenza, and dengue virus. Among the 284 enrolled patients, 31 dengue, 136 influenza, and 3 enterovirus cases were confirmed. Nearly half (48%) of the confirmed dengue cases met clinical criteria for influenza. Dengue patients were more likely than influenza patients to have hemorrhage (81% versus 26%), rash (39% versus 9%), and a positive tourniquet test (52% versus 18%). Mean platelet and white blood cell count were lower among dengue patients. Clinical diagnosis can be particularly difficult when outbreaks of other AFI occur during dengue season. A complete blood count and tourniquet test may be useful to differentiate dengue from other AFIs. PMID:23382160

  10. Acute febrile illness surveillance in a tertiary hospital emergency department: comparison of influenza and dengue virus infections.

    PubMed

    Lorenzi, Olga D; Gregory, Christopher J; Santiago, Luis Manuel; Acosta, Héctor; Galarza, Ivonne E; Hunsperger, Elizabeth; Muñoz, Jorge; Bui, Duy M; Oberste, M Steven; Peñaranda, Silvia; García-Gubern, Carlos; Tomashek, Kay M

    2013-03-01

    In 2009, an increased proportion of suspected dengue cases reported to the surveillance system in Puerto Rico were laboratory negative. As a result, enhanced acute febrile illness (AFI) surveillance was initiated in a tertiary care hospital. Patients with fever of unknown origin for 2-7 days duration were tested for Leptospira, enteroviruses, influenza, and dengue virus. Among the 284 enrolled patients, 31 dengue, 136 influenza, and 3 enterovirus cases were confirmed. Nearly half (48%) of the confirmed dengue cases met clinical criteria for influenza. Dengue patients were more likely than influenza patients to have hemorrhage (81% versus 26%), rash (39% versus 9%), and a positive tourniquet test (52% versus 18%). Mean platelet and white blood cell count were lower among dengue patients. Clinical diagnosis can be particularly difficult when outbreaks of other AFI occur during dengue season. A complete blood count and tourniquet test may be useful to differentiate dengue from other AFIs.

  11. Acute febrile illness surveillance in a tertiary hospital emergency department: comparison of influenza and dengue virus infections.

    PubMed

    Lorenzi, Olga D; Gregory, Christopher J; Santiago, Luis Manuel; Acosta, Héctor; Galarza, Ivonne E; Hunsperger, Elizabeth; Muñoz, Jorge; Bui, Duy M; Oberste, M Steven; Peñaranda, Silvia; García-Gubern, Carlos; Tomashek, Kay M

    2013-03-01

    In 2009, an increased proportion of suspected dengue cases reported to the surveillance system in Puerto Rico were laboratory negative. As a result, enhanced acute febrile illness (AFI) surveillance was initiated in a tertiary care hospital. Patients with fever of unknown origin for 2-7 days duration were tested for Leptospira, enteroviruses, influenza, and dengue virus. Among the 284 enrolled patients, 31 dengue, 136 influenza, and 3 enterovirus cases were confirmed. Nearly half (48%) of the confirmed dengue cases met clinical criteria for influenza. Dengue patients were more likely than influenza patients to have hemorrhage (81% versus 26%), rash (39% versus 9%), and a positive tourniquet test (52% versus 18%). Mean platelet and white blood cell count were lower among dengue patients. Clinical diagnosis can be particularly difficult when outbreaks of other AFI occur during dengue season. A complete blood count and tourniquet test may be useful to differentiate dengue from other AFIs. PMID:23382160

  12. Liver function test results and outcomes in children with acute liver failure due to dengue infection.

    PubMed

    Chongsrisawat, Voranush; Hutagalung, Yanee; Poovorawan, Yong

    2009-01-01

    This retrospective study compared the liver function test results and outcomes between children with acute liver failure (ALF) due to dengue hemorrhagic fever (DHF) and due to other causes. We retrospectively reviewed patients less than 15 years old with a diagnosis of ALF admitted to 13 participating centers from different parts of Thailand for the years 2000 and 2001, and those admitted to King Chulalongkorn Memorial Hospital for the year 1997 to 2004. The diagnosis of ALF was based on prothrombin time (PT) prolongation to greater than 2 times the normal control value and the presence of encephalopathy without pre-existing liver disease. The patients were divided into 2 groups: group I (n=16) had DHF with ALF and group II (n=37) had ALF due to other causes. DHF patients had AST levels significantly higher than ALT levels. The mortality rate in group I (50%) was lower than in group II (72.9%), although the difference was not statistically significant. The non-DHF patients who died had a significantly longer duration of jaundice before the onset of encephalopathy and a significantly higher PT ratio compared to survivors. There were no significant differences in the duration of jaundice before the onset of encephalopathy and liver function between dengue patients who died and those who survived.

  13. Dengue infection: a global concern.

    PubMed

    Pancharoen, Chitsanu; Kulwichit, Wanla; Tantawichien, Terapong; Thisyakorn, Usa; Thisyakorn, Chule

    2002-06-01

    Dengue infection, one of the most important mosquito-borne viral diseases of humans, is now a significant problem in several tropical countries. The disease, caused by the four dengue virus serotypes, ranges from asymptomatic infection, undifferentiated fever, dengue fever (DF) to severe dengue hemorrhagic fever (DHF) with or without shock. DHF is characterized by fever, bleeding diathesis and a tendency to develop a potentially fatal shock syndrome. Hematological findings include vasculopathy, coagulopathy and thrombocytopenia as the most constant findings. During the last twenty-five years, there have been increasing reports of dengue infection with unusual manifestations, mainly with cerebral and hepatic symptoms. Laboratory diagnosis includes virus isolation, serology and detection of dengue ribonucleic acid. Successful treatment, which is mainly supportive, depends on early recognition of the disease and careful monitoring for shock. Prevention depends on control of the mosquito vector. More efforts must be made to understand the pathogenesis of DHF in order to develop a safe and effective dengue vaccine.

  14. Dengue infections in HIV patients.

    PubMed

    Siong, Wong Chia; Ching, Tan Huey; Jong, Go Chi; Pang, Chan Siew; Vernon, Lee Jian Ming; Sin, Leo Yee

    2008-03-01

    A retrospective review of hospital admission records was conducted on patients who were admitted to the Communicable Disease Center (CDC)/Tan Tock Seng Hospital, Singapore from 1 January 2004 to 31 December 2005. There were 5 HIV patients who were admitted with dengue infection during the study period. Their symptoms were generally mild and recovery was uneventful. None of the patients developed dengue hemorrhagic fever or dengue shock syndrome. The symptoms and signs of dengue infection in HIV patients are nonspecific. It is important for healthcare workers to maintain a high index of suspicion in order to make the diagnosis. Interactions between pathogenesis pathways or with antiviral treatments may have contributed to the apparently less severe dengue infections in HIV patients. This observation needs to be explored further.

  15. Evaluation of six commercial point-of-care tests for diagnosis of acute dengue infections: the need for combining NS1 antigen and IgM/IgG antibody detection to achieve acceptable levels of accuracy.

    PubMed

    Blacksell, Stuart D; Jarman, Richard G; Bailey, Mark S; Tanganuchitcharnchai, Ampai; Jenjaroen, Kemajittra; Gibbons, Robert V; Paris, Daniel H; Premaratna, Ranjan; de Silva, H Janaka; Lalloo, David G; Day, Nicholas P J

    2011-12-01

    Six assays were evaluated in this study to determine their suitability for the diagnosis of acute dengue infection using samples from 259 Sri Lankan patients with acute fevers (99 confirmed dengue cases and 160 patients with other confirmed acute febrile illnesses): (i) the Merlin dengue fever IgG & IgM combo device (Merlin), (ii) the Standard Diagnostics Dengue Duo nonstructural 1 (NS1) antigen and IgG/IgM combo device (Standard Diagnostics, South Korea), (iii) the Biosynex Immunoquick dengue fever IgG and IgM (Biosynex, France) assay, (iv) the Bio-Rad NS1 antigen strip (Bio-Rad, France), (v) the Panbio Dengue Duo IgG/IgM Cassette (Inverness, Australia), and (vi) the Panbio dengue NS1 antigen strip (Inverness, Australia). The median number of days of fever prior to admission sample collection was 5 days (interquartile range, 3 to 7 days). Sensitivity and specificity of the NS1 antigen tests ranged from 49 to 59% and from 93 to 99%, respectively, and sensitivity and sensitivity of the IgM antibody test ranged from 71 to 80% and from 46 to 90%, respectively. Combining the NS1 antigen and IgM antibody results from the Standard Diagnostics Dengue Duo test gave the best compromise of sensitivity and specificity (93% and 89%, respectively) and provided the best sensitivity in patients presenting at different times after fever onset. The Merlin IgM/IgG antibody tests correctly classified 64% and 86% of the primary and secondary dengue infection cases, respectively, and the Standard Diagnostics IgM/IgG antibody tests correctly classified 71% and 83% of the primary and secondary dengue infection cases, respectively. This study provides strong evidence of the value of combining dengue antigen- and antibody-based test results in the rapid diagnostic test (RDT) format for the acute diagnosis of dengue.

  16. 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

  17. [Virology diagnosis of re-emergent infections: dengue virus].

    PubMed

    Vilibić-Cavlek, Tatjana; Ljubin-Sternak, Suncanica; Babić-Erceg, Andrea; Sviben, Mario; Mlinarić-Galinović, Gordana

    2012-01-01

    Dengue is acute viral disease transmitted to humans by Aedes mosquitoes (Ae. aegypti, Ae. albopictus). Dengue virus belongs to the family Flaviviridae, genus Flavivirus. There are four dengue virus serotypes (1-4) which are maintained endemically. The disease is endemic in tropical and subtropical areas between latitudes 35 degrees N and 35 degrees S. Infections may be asymptomatic or may produce a wide spectrum of diseases: non-specific febrile illness, dengue fever, dengue haemorrhagic fever or dengue shock syndrome. For the first time in Croatia, Ae. albopictus was registered in Zagreb in October 2004. In autumn 2005, additional records of Ae. albopictus presence were made in many places along the Adriatic coast. During 2007, two cases of imported dengue fever were reported in Croatia, after which similar imported cases appeared continually. In August 2010, the first autochthonous case of dengue fever was recorded on the peninsula Peljesac. Though Croatia is not endemic for dengue, the existence of a corresponding vector and a latent threat by imported dengue cases demand state-of-the-art and timely diagnostics. The most commonly used methods in laboratory diagnosis of dengue infections involve detection of viral RNA, antigen detection and serologic methods (detection of antibodies).

  18. Inducible nitric oxide synthase (iNOS) expression in monocytes during acute Dengue Fever in patients and during in vitro infection

    PubMed Central

    Neves-Souza, Patrícia CF; Azeredo, Elzinandes L; Zagne, Sonia MO; Valls-de-Souza, Rogério; Reis, Sonia RNI; Cerqueira, Denise IS; Nogueira, Rita MR; Kubelka, Claire F

    2005-01-01

    Abstract Mononuclear phagocytes are considered to be main targets for Dengue Virus (DENV) replication. These cells are activated after infection, producing proinflammatory mediators, including tumour-necrosis factor-α, which has also been detected in vivo. Nitric oxide (NO), usually produced by activated mononuclear phagocytes, has antimicrobial and antiviral activities. Methods The expression of DENV antigens and inducible nitric oxide synthase (iNOS) in human blood isolated monocytes were analysed by flow cytometry using cells either from patients with acute Dengue Fever or after DENV-1 in vitro infection. DENV-1 susceptibility to iNOS inhibition and NO production was investigated using NG-methyl L-Arginine (NGMLA) as an iNOS inhibitor, which was added to DENV-1 infected human monocytes, and sodium nitroprussiate (SNP), a NO donor, added to infected C6/36 mosquito cell clone. Viral antigens after treatments were detected by flow cytometry analysis. Results INOS expression in activated monocytes was observed in 10 out of 21 patients with Dengue Fever and was absent in cells from ten healthy individuals. DENV antigens detected in 25 out of 35 patients, were observed early during in vitro infection (3 days), significantly diminished with time, indicating that virus replicated, however monocytes controlled the infection. On the other hand, the iNOS expression was detected at increasing frequency in in vitro infected monocytes from three to six days, exhibiting an inverse relationship to DENV antigen expression. We demonstrated that the detection of the DENV-1 antigen was enhanced during monocyte treatment with NGMLA. In the mosquito cell line C6/36, virus detection was significantly reduced in the presence of SNP, when compared to that of untreated cells. Conclusion This study is the first to reveal the activation of DENV infected monocytes based on induction of iNOS both in vivo and in vitro, as well as the susceptibility of DENV-1 to a NO production. PMID:16109165

  19. Models of dengue virus infection.

    PubMed

    Bente, Dennis A; Rico-Hesse, Rebeca

    2006-01-01

    The need for models of dengue disease has reached a pinnacle as the transmission of this mosquito-borne virus has increased dramatically. Little is known about the mechanisms that lead to dengue fever and its more severe form, dengue hemorrhagic fever; this is owing to the fact that only humans show signs of disease. In the past 5 years, research has better identified the initial target cells of infection, and this has led to the development of models of infection in primary human cell cultures. Mouse-human chimeras, containing these target cells, have also led to progress in developing animal models. These advances should soon end the stalemate in testing antivirals and vaccine preparations that had necessarily been done in incomplete or irrelevant models. PMID:18087566

  20. Secondary dengue virus type 4 infections in Vietnam.

    PubMed

    Buchy, Philippe; Vo, Van Luong; Bui, Khanh Toan; Trinh, Thi Xuan Mai; Glaziou, Philippe; Le, Thi Thu Ha; Le, Viet Lo; Bui, Trong Chien

    2005-01-01

    This study was designated to describe clinical and biological features of patients with a suspected diagnosis of dengue fever/dengue hemorrhagic fever during an outbreak in Central Vietnam. One hundred and twenty-five consecutive patients hospitalized at Khanh Hoa and Binh Thuan Provincial hospitals between November 2001 and January 2002 with a diagnosis of suspected dengue infection were included in the present study. Viruses were isolated in C6/36 and VERO E6 cell cultures or detected by RT-PCR. A hemagglutination-inhibition test (HI) was done on each paired sera using dengue antigens type 1-4, Japanese encephalitis (JE) virus antigen, Chickungunya virus antigen and Sindbis virus antigen. Anti-dengue and anti-JE virus IgM were measured by a capture enzyme-linked immunosorbent assay (MAC-ELISA). Anti-dengue and anti-JE virus IgG were measured by an ELISA test. Dengue viruses were isolated in cell culture and/or detected by RT-PCR in 20.8% of blood samples. DEN-4 and DEN-2 serotypes were found in 18.4% and 2.4% of the patients, respectively. A total of 86.4% of individuals had a diagnosis of acute dengue fever by using the HI test and/or dengue virus-specific IgM capture-ELISA and/or virus isolation and/or RT-PCR. The prevalence of primary and secondary acute dengue infection was 4% and 78.4%, respectively. Anti-dengue IgG ELISA test was positive in 88.8% of the patients. In 5 cases (4%), Japanese encephalitis virus infection was positive by serology but the cell culture was negative. No Chickungunya virus or Sindbis virus infection was detected by the HI test. In patients with acute dengue virus infection, the most common presenting symptom was headache, followed by conjunctivitis, petechial rash, muscle and joint pain, nausea and abdominal pain. Four percent of hospitalized patients were classified as dengue hemorrhagic fever. The clinical presentation and blood cell counts were similar between patients hospitalized with acute dengue fever and patients with other

  1. Dengue infection presenting with central nervous system manifestation.

    PubMed

    Kankirawatana, P; Chokephaibulkit, K; Puthavathana, P; Yoksan, S; Apintanapong, S; Pongthapisit, V

    2000-08-01

    The objective of this study was to investigate the possibility of dengue virus infection causing an abnormal neurologic presentation. Between 1996 and 1998, all pediatric patients with clinical manifestations of encephalitis-like illness who were admitted to the Department of Pediatrics, Siriraj Hospital were prospectively studied for any evidence of dengue virus infection. The diagnosis of dengue virus infection was based on mosquito viral isolation and serologic and polymerase chain reaction (PCR) evidence. Of 44 patients with the preliminary diagnosis of acute viral encephalitis, 8 were diagnosed with dengue infection. All of these 8 patients were diagnosed by serology. In addition to the serologic diagnosis, four also had positive PCR, one had positive viral isolation, and one had both positive PCR and viral isolation. Only two patients were diagnosed by serologic evidence alone. All except one had clinical courses and laboratory findings compatible with typical dengue infection. All had obvious encephalitic clinical manifestations with normal cerebrospinal fluid findings except one patient, who had mildly increased cerebrospinal fluid protein. All of these patients recovered completely and had benign clinical courses except one patient, who developed leakage symptoms. None had liver failure. Dengue virus can cause acute encephalopathy with fever. It can masquerade as other types of acute viral encephalitis. However, its clinical course and prognosis are usually favorable.

  2. Hepatic dysfunction in childhood dengue infection.

    PubMed

    Mohan, B; Patwari, A K; Anand, V K

    2000-02-01

    Hepatic functions of 61 children, diagnosed to have dengue infection (DI), aged 2 months to 12 years comprising 37 cases of dengue fever (DF), 16 with dengue hemorrhagic fever (DHF), and eight with dengue shock syndrome (DSS) were prospectively studied during the acute attack. Hepatomegaly (74 per cent), epistaxis (26 per cent), jaundice (25 per cent), and petechial rashes (18 per cent) were the common clinical manifestations of DI. On admission, levels of serum aspartate transaminase (AST), serum alanine transaminase (ALT) and serum alkaline phosphatase (AP) were raised in 80-87 per cent of children with hepatomegaly (group I) and 81 per cent of cases without hepatomegaly (group II). During the second week of hospitalization the proportion of cases with raised levels of AST, ALT, AP and serum bilirubin increased and the mean levels were significantly higher (p < 0.05) in both the groups. These levels gradually declined over the next 2-3 weeks. All the cases with DSS and DHF had raised AST, ALT and AP levels and the mean levels of these enzymes were significantly higher (p < 0.05) as compared to DF. Our results suggest a transient derangement of liver functions in childhood DI, more so in DSS and DHF, with or without hepatomegaly.

  3. Comparison of dengue virus antigens in sera and peripheral blood mononuclear cells from dengue infected patients.

    PubMed

    Kittigul, L; Meethien, N; Sujirarat, D; Kittigul, C; Vasanavat, S

    1997-12-01

    The presence of dengue virus antigens in acute sera and peripheral blood mononuclear cells (PBMC) from dengue infected patients were determined by a biotin-streptavidin enzyme-linked immunosorbent assay (BS-ELISA). The frequency of the antigens detected in PBMC was higher than that in sera (53.8% vs 18.9%). In comparison with sera, the detection rate in PBMC was greater than six times: 7 cases were positive only in sera whereas 44 cases were positive only in PBMC, p < 0.001. The presence of the antigens in the sera did not depend on the severity of the disease, i.e. dengue fever, dengue hemorrhagic fever (grades I and II) or dengue shock syndrome (grades III and IV). In contrast, the presence of the antigens in PBMC increased from 36.8% to 100% when the infection was more severe. The dengue virus antigens could be detected in the samples collected between day 2 and day 7 after onset of the disease with the highest rate of detection (68.8%) in PBMC collected on day 4. The data suggest the use of PBMC with access to the appropriate acute-phase specimen for detection of dengue virus antigens.

  4. Dengue infection: a growing global health threat.

    PubMed

    Hemungkorn, Marisa; Thisyakorn, Usa; Thisyakorn, Chule

    2007-10-01

    Dengue infection, one of the most devastating mosquito-borne viral diseases in humans, is now a significant problem in several tropical countries. The disease, caused by the four dengue virus serotypes, ranges from asymptomatic infection to undifferentiated fever, dengue fever (DF), and severe dengue hemorrhagic fever (DHF) with or without shock. DHF is characterized by fever, bleeding diathesis and a tendency to develop a potentially fatal shock syndrome. Consistent hematological findings include vasculopathy, coagulopathy, and thrombocytopenia. There are increasing reports of dengue infection with unusual manifestations that mainly involve cerebral and hepatic symptoms. Laboratory diagnosis includes virus isolation, serology, and detection of dengue ribonucleic acid. Successful treatment, which is mainly supportive, depends on early recognition of the disease and careful monitoring for shock. Prevention depends primarily on control of the mosquito vector. Further study of the pathogenesis of DHF is required for the development of a safe and effective dengue vaccine.

  5. Competitive inhibitor of cellular α-glucosidases protects mice from lethal dengue virus infection.

    PubMed

    Chang, Jinhong; Schul, Wouter; Yip, Andy; Xu, Xiaodong; Guo, Ju-Tao; Block, Timothy M

    2011-11-01

    Dengue virus infection causes diseases in people, ranging from the acute febrile illness dengue fever, to life-threatening dengue hemorrhagic fever/dengue shock syndrome. We previously reported that a host cellular α-glucosidases I and II inhibitor, imino sugar CM-10-18, potently inhibited dengue virus replication in cultured cells, and significantly reduced viremia in dengue virus infected AG129 mice. In this report we show that CM-10-18 also significantly protects mice from death and/or disease progress in two mouse models of lethal dengue virus infection. Our results thus provide a strong support for the development of CM-10-18 or its derivatives as antiviral agents to treat servere dengue virus infections.

  6. Imported dengue virus infections in German tourists.

    PubMed

    Schwarz, T F; Jäger, G; Gilch, S

    1995-10-01

    Dengue viruses (DEN) are increasingly becoming endemic and epidemic in tropical and subtropical countries. In this study, 17 serologically confirmed clinical cases of DEN infection diagnosed in German tourists over the period from May 1993 until May 1994 are presented. Thirteen out of 17 (76.5%) infections occurred in southeast Asia (Thailand 58.9%), and 4/17 (23.5%) in Central and South America. All sera screened by means of the indirect immunofluorescence assay (IIFA) were positive for anti-DEN IgM. Acute infection was confirmed by demonstrating anti-DEN IgM using a "mu-capture assay". Sixteen out of 17 (94.1%) of patients presenting with fever upon admission were positive for anti-DEN IgG, with titres of > or = 128 in the IIFA. This report indicates the rising significance of DEN as a travel-associated infection in German tourists.

  7. Serodiagnosis of dengue virus infection in patients presenting to a tertiary care hospital.

    PubMed

    Neeraja, M; Lakshmi, V; Teja, V D; Umabala, P; Subbalakshmi, M V

    2006-10-01

    Dengue is an acute infectious disease of viral etiology. It is probably one of the most important arthropod borne viral disease in terms of human morbidity and mortality. The spectrum of disease ranges from self-limited dengue fever to more severe forms of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Laboratory diagnosis of dengue virus infection mainly depends on detection of virus specific antibodies. The aim of the study was to correlate the serological results with clinical presentation in patients with a diagnosis of dengue. Eleven out of 15 (73.3%) patients with DHF and DSS had secondary antibody response and mortality was 100% in these patients.

  8. Evaluation of the diagnostic accuracy of a new dengue IgA capture assay (Platelia Dengue IgA Capture, Bio-Rad) for dengue infection detection.

    PubMed

    De Decker, Sophie; Vray, Muriel; Sistek, Viridiana; Labeau, Bhety; Enfissi, Antoine; Rousset, Dominique; Matheus, Séverine

    2015-03-01

    Considering the short lifetime of IgA antibodies in serum and the key advantages of antibody detection ELISAs in terms of sensitivity and specificity, Bio-Rad has just developed a new ELISA test based on the detection of specific anti-dengue IgA. This study has been carried out to assess the performance of this Platelia Dengue IgA Capture assay for dengue infection detection. A total of 184 well-characterized samples provided by the French Guiana NRC sera collection (Laboratory of Virology, Institut Pasteur in French Guiana) were selected among samples collected between 2002 and 2013 from patients exhibiting a dengue-like syndrome. A first group included 134 sera from confirmed dengue-infected patients, and a second included 50 sera from non-dengue infected patients, all collected between day 3 and day 15 after the onset of fever. Dengue infection diagnoses were all confirmed using reference assays by direct virological identification using RT-PCR or virus culture on acute sera samples or on paired acute-phase sera samples of selected convalescent sera. This study revealed: i) a good overall sensitivity and specificity of the IgA index test, i.e., 93% and 88% respectively, indicating its good correlation to acute dengue diagnosis; and ii) a good concordance with the Panbio IgM capture ELISA. Because of the shorter persistence of dengue virus-specific IgA than IgM, these results underlined the relevance of this new test, which could significantly improve dengue diagnosis accuracy, especially in countries where dengue virus is (hyper-) endemic. It would allow for additional refinement of dengue diagnostic strategy.

  9. Dengue shock syndrome in an American traveler with primary dengue 3 infection.

    PubMed

    Morens, D M; Sather, G E; Gubler, D J; Rammohan, M; Woodall, J P

    1987-03-01

    A previously reported case of childhood dengue shock syndrome in an American traveler to India was investigated serologically. The original studies neither indicated the infecting serotype nor proved primary or secondary infection. However, BHK suspension PRNT of 6-year convalescent serum now indicates that the child had primary dengue type 3 infection. Dengue, dengue hemorrhagic fever, and dengue shock syndrome are potential hazards for American travelers and American residents of dengue-receptive areas.

  10. 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. PMID:26424605

  11. 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.

  12. Desialylation of plasma proteins in severe dengue infection: possible role of oxidative stress.

    PubMed

    Rajendiran, Soundravally; Lakshamanappa, Hoti Sugeerappa; Zachariah, Bobby; Nambiar, Selvaraj

    2008-09-01

    Oxidative stress in dengue infection has been suggested. This study was carried out to explore the plasma protein oxidation and its sialic acid content in dengue infection. Thirty-two dengue hemorrhagic fever (DHF), 25 dengue shock syndrome (DSS), 29 dengue fever (DF), and 63 healthy controls were included in this study. The extent of carbonylation, sulphydryl content, and desialylation of plasma protein was estimated in acute phase sample. Significantly higher levels of protein carbonyls and lower levels of sialic acid and sulphydryl groups were found in DHF and DSS compared with DF using one-way analysis of variance. Regression analysis showed that desialylation is dependent on protein carbonyls in DHF/DSS. This study indicates that, in dengue infection, plasma proteins undergo increased levels of desialylation, which can be attributed to the oxidative stress. Future studies on sialylation status of endothelium and platelets can show light into the pathogenesis of the dengue infection.

  13. Immune complex: does it have a role in pathogenesis of renal failure in dengue infection?

    PubMed

    Wiwanitkit, Viroj

    2005-01-01

    Dengue infection is a major public health problem. When acute renal failure complicates dengue infection, it is usually associated with severe disease as in dengue hemorrhagic fever or dengue shock syndrome. The role of immune complex in development of renal failure in dengue infection is still unclear. Here, the author used a computational medicine technology to study the property of the dengue virus-immunoglobulin complex. According to this study, the diameter of derived complex is much smaller, compared with the diameter of glomerulus. Entrapment of the immune complex is believed to occur when a previous glomerular lesion causes narrowing of the glomerulus's diameter. Therefore, the immune complex should not have a significant role in pathogenesis of renal failure in dengue infection.

  14. Development of dengue infection severity score.

    PubMed

    Pongpan, Surangrat; Wisitwong, Apichart; Tawichasri, Chamaiporn; Patumanond, Jayanton; 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 / μ L, and platelet ≤50000 / μ L. 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.

  15. 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

  16. 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

  17. Microglia retard dengue virus-induced acute viral encephalitis

    PubMed Central

    Tsai, Tsung-Ting; Chen, Chia-Ling; Lin, Yee-Shin; Chang, Chih-Peng; Tsai, Cheng-Chieh; Cheng, Yi-Lin; Huang, Chao-Ching; Ho, Chien-Jung; Lee, Yi-Chao; Lin, Liang-Tzung; Jhan, Ming-Kai; Lin, Chiou-Feng

    2016-01-01

    Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV-infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice. In microglia-depleted mice, the DENV infection-mediated expression of antiviral cytokines and the infiltration of CD8-positive cytotoxic T lymphocytes (CTLs) was abolished. DENV infection prompted the antigen-presenting cell-like differentiation of microglia, which in turn stimulated CTL proliferation and activation. These results suggest that microglial cells play a key role in facilitating antiviral immune responses against DENV infection and acute viral encephalitis. PMID:27279150

  18. Microglia retard dengue virus-induced acute viral encephalitis.

    PubMed

    Tsai, Tsung-Ting; Chen, Chia-Ling; Lin, Yee-Shin; Chang, Chih-Peng; Tsai, Cheng-Chieh; Cheng, Yi-Lin; Huang, Chao-Ching; Ho, Chien-Jung; Lee, Yi-Chao; Lin, Liang-Tzung; Jhan, Ming-Kai; Lin, Chiou-Feng

    2016-01-01

    Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV-infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice. In microglia-depleted mice, the DENV infection-mediated expression of antiviral cytokines and the infiltration of CD8-positive cytotoxic T lymphocytes (CTLs) was abolished. DENV infection prompted the antigen-presenting cell-like differentiation of microglia, which in turn stimulated CTL proliferation and activation. These results suggest that microglial cells play a key role in facilitating antiviral immune responses against DENV infection and acute viral encephalitis. PMID:27279150

  19. Dengue viral infections as a cause of encephalopathy.

    PubMed

    Malavige, G N; Ranatunga, P K; Jayaratne, S D; Wijesiriwardana, B; Seneviratne, S L; Karunatilaka, D H

    2007-04-01

    The aim of this study was to determine the clinical characteristics and poor prognostic factors associated with high mortality in dengue encephalopathy. Fifteen patients with confirmed dengue infections, who developed encephalopathy, were recruited from two tertiary care hospitals in Colombo, Sri Lanka. Among the factors that contributed to encephalopathy were: Acute liver failure (73%), electrolyte imbalances (80%) and shock (40%). Five (33.3%) patients developed seizures. Disseminated intravascular coagulation was seen in five (33.3%). Secondary bacterial infections were observed in 8 (53.3%) of our patients. The overall mortality rate was 47%.

  20. Epidemiological and clinical features of dengue versus other acute febrile illnesses amongst patients seen at government polyclinics.

    PubMed

    Mustafa, B; Hani, A W Asmah; Chem, Y K; Mariam, M; Khairul, A H; Abdul Rasid, K; Chua, K B

    2010-12-01

    Classical dengue fever is characterized by the clinical features of fever, headache, severe myalgia and occasionally rash, which can also be caused by a number of other viral and bacterial infections. Five hundred and fifty eight patients who fulfilled the criteria of clinical diagnosis of acute dengue from 4 government outpatient polyclinics were recruited in this prospective field study. Of the 558 patients, 190 patients were categorized as acute dengue fever, 86 as recent dengue and 282 as non-dengue febrile illnesses based on the results of a number of laboratory tests. Epidemiological features of febrile patients showed that the mean age of patients in the dengue fever group was significantly younger in comparison with patients in the non-dengue group. There was no significant difference between the two groups with respect to gender but there was significant ethnic difference with foreign workers representing a higher proportion in the dengue fever group. Patients with acute dengue fever were more likely to have patient-reported rash and a history of dengue in family or neighbourhood but less likely to have respiratory symptoms, sore-throat and jaundice in comparison to patients with non-dengue febrile illnesses. As with patients with dengue fever, patients in the recent dengue group were more likely to have history of patient-reported rash and a history of dengue contact and less likely to have respiratory symptoms in comparison to patients with non-dengue febrile illnesses. In contrast to patients with dengue fever, patients in the recent dengue group were more likely to have abdominal pain and jaundice in comparison to non-dengue febrile patients. The finding strongly suggests that a proportion of patients in the recent dengue group may actually represent a subset of patients with acute dengue fever at the late stage of illness.

  1. Temporal distribution of dengue virus serotypes in Colombian endemic area and dengue incidence. Re-introduction of dengue-3 associated to mild febrile illness and primary infection.

    PubMed

    Ocazionez, Raquel Elvira; Cortés, Fabián Mauricio; Villar, Luis Angel; Gómez, Sergio Yebrail

    2006-11-01

    We have investigated the temporal distribution of dengue (DEN) virus serotypes in the department (state) of Santander, Colombia, in relation to dengue incidence, infection pattern, and severity of disease. Viral isolation was attended on a total of 1452 acute serum samples collected each week from 1998 to 2004. The infection pattern was evaluated in 596 laboratory-positive dengue cases using an IgG ELISA, and PRNT test. The dengue incidence was documented by the local health authority. Predominance of DEN-1 in 1998 and DEN-3 re-introduction and predominance in 2001-2003 coincided with outbreaks. Predominance of DEN-2 in 2000-2001 coincided with more dengue hemorrhagic fever (DHF). DEN-4 was isolated in 2000-2001 and 2004 but was not predominant. There was an annual increase of primary dengue infections (from 13.7 to 81.4%) that correlated with frequency of DEN-3 (r = 0.83; P = 0.038). From the total number of primary dengue infections DEN-3 (81.3%) was the most frequent serotype. DHF was more frequent in DEN-2 infected patients than in DEN-3 infected patients: 27.5 vs 10.9% (P < 0.05). DEN-3 viruses belonged to subtype C (restriction site-specific-polymerase chain reaction) like viruses isolated in Sri-Lanka and other countries in the Americas. Our findings show the importance of continuous virological surveillance to identify the risk factors of dengue epidemics and severity.

  2. Early detection of dengue infections using cluster sampling around index cases.

    PubMed

    Beckett, Charmagne G; Kosasih, Herman; Faisal, Indra; Nurhayati; Tan, Ratna; Widjaja, Susana; Listiyaningsih, Erlin; Ma'roef, Chairin; Wuryadi, Suharyono; Bangs, Michael J; Samsi, Tatang K; Yuwono, Djoko; Hayes, Curtis G; Porter, Kevin R

    2005-06-01

    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 volunteers enrolled, 17 (2.2%) post-enrollment dengue (PED) infections were identified. Eight PED cases were asymptomatic and nine were symptomatic. Symptomatic cases included eight with dengue fever and one with dengue hemorrhagic fever (DHF) (grade II). Among the eight asymptomatic PED cases, viremia was detected in two. Eleven volunteers had acute dengue infections at the time of enrollment. Four of the 11 developed DHF, resulting in a total of five DHF cases detected during the investigation. This study design can serve as a benchmark for future investigations that seek to define early immunologic events following dengue infections that contribute to the development of DHF.

  3. DENGUE INFECTION IN ELDERLY PATIENTS.

    PubMed

    Tiawilai, Thawat; Tiawilai, Anongrat; Nunthanid, Somboon

    2015-01-01

    From 2005 to 2013, there were 15 dengue patients aged over 60 years old who were admitted to Photharam Hospital, Ratchaburi, Thailand. Ten were females and five were males. Nine had dengue fever (DF), and 6 had dengue hemorrhagic fever (DHF). A trending shift in age group towards adults has been seen during the past decades. No deaths were seen in these elderly patients with dengue disease, indicating early recognition and effective management of these dengue patients. The trend towards higher age in dengue patients is a problem of concern, which needs further elaboration.

  4. 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

  5. Human dendritic cells as targets of dengue virus infection.

    PubMed

    Marovich, M; Grouard-Vogel, G; Louder, M; Eller, M; Sun, W; Wu, S J; Putvatana, R; Murphy, G; Tassaneetrithep, B; Burgess, T; Birx, D; Hayes, C; Schlesinger-Frankel, S; Mascola, J

    2001-12-01

    Dengue virus infections are an emerging global threat. Severe dengue infection is manifested as dengue hemorrhagic fever and dengue shock syndrome, both of which can be fatal complications. Factors predisposing to complicated disease and pathogenesis of severe infections are discussed. Using immunohistochemistry, immunofluorescence, flow cytometry, and ELISA techniques, we studied the cellular targets of dengue virus infection, at both the clinical (in vivo) and the laboratory (in vitro) level. Resident skin dendritic cells are targets of dengue virus infection as demonstrated in a skin biopsy from a dengue vaccine recipient. We show that factors influencing infection of monocytes/macrophages and dendritic cells are different. Immature dendritic cells were found to be the cells most permissive for dengue infection and maybe early targets for infection. Immature dendritic cells exposed to dengue virus produce TNF-alpha protein. Some of these immature dendritic cells undergo TNF-alpha mediated maturation as a consequence of exposure to the dengue virus. PMID:11924831

  6. Headache features in patients with dengue virus infection.

    PubMed

    Domingues, R B; Kuster, G W; Onuki de Castro, F L; Souza, V A; Levi, J E; Pannuti, C S

    2006-07-01

    The aim of this study was to describe the frequency and features of headache among patients with confirmed dengue virus infection and to compare the headache features in patients with dengue fever and dengue haemorrhagic fever, primary and secondary dengue infection, and patients with and without neurological involvement. Patients with classic dengue fever had a more intense headache than those with the more severe form of the disease, dengue haemorrhagic fever.

  7. 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

  8. 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 ...

  9. Dengue virus isolation by antibody-dependent enhancement of infectivity in macrophages.

    PubMed

    Cardosa, M J

    1987-01-24

    Acute-phase serum samples collected during an outbreak of dengue fever and dengue haemorrhagic fever in Penang, Malaysia, were tested by a method involving antibody-dependent enhancement of infectivity in the mouse macrophage-like cell line, P388D1. 58 of 71 (81.7%) serologically positive cases yielded virus.

  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. Dengue fever with acute acalculous cholecystitis.

    PubMed

    Wu, Keng-Liang; Changchien, Chi-Sin; Kuo, Chung-Mou; Chuah, Seng-Kee; Lu, Sheng-Nan; Eng, Hock-Liew; Kuo, Chung-Huang

    2003-06-01

    Dengue fever (DF) with acute acalculous cholecystitis is rarely reported. To investigate the incidence, treatment, and prognosis of acute acalculous cholecystitis in DF patients, we retrospectively studied 10 patients with DF and acute acalculous cholecystitis. From October 2001 to July 2002, 131 patients were diagnosed with DF. Ten of 131 DF patients (7.63%) had complications of acute acalculous cholecystitis. Two patients underwent cholecystectomy and one underwent percutaneous transhepatic gallbladder drainage due to poor resolution of acute acalculous cholecystitis. We found acute acalculous cholecystitis in a small proportion of patients with DF. In our experience, closely monitoring vital signs to avoid shock and correct thrombocytopenia to avoid bleeding could be adequate for most patients. In some cases, surgical treatment may be needed for DF fever patients with complications of diffuse peritonitis.

  12. Dengue viral infections; pathogenesis and epidemiology.

    PubMed

    McBride, W J; Bielefeldt-Ohmann, H

    2000-07-01

    Dengue viral infections affect up to 100 million individuals per year. Dengue haemorrhagic fever is a clinical form of disease characterised by intravascular fluid loss. There has been a marked increase in the incidence of this form of the disease over the last few decades, associated with significant mortality, particularly in the paediatric population. A number of theories relating to the pathogenesis of dengue haemorrhagic fever exist that have evolved from the analysis of the epidemiology of this disease. Virological and immunopathological factors are both important but the exact mechanisms for the disease are unknown.

  13. Application of revised dengue classification criteria as a severity marker of dengue viral infection in Indonesia.

    PubMed

    Basuki, Parwati Setiono; Budiyanto; Puspitasari, Dwiyanti; Husada, Dominicus; Darmowandowo, Widodo; Ismoedijanto; Soegijanto, Soegeng; Yamanaka, Atsushi

    2010-09-01

    A prospective study of dengue infected patients at Dr.Soetomo Hospital pediatric ward was carried out from October 2008 to April 2009 to evaluate the revised dengue classification system proposed by the Dengue Control (DENCO), for early detection of severe dengue infected patients using the WHO classification system for comparison, with the addition of clinical interventions as a tool to grade for severity. One hundred forty-five patients were included in the study. Using the WHO classification system, 122 cases (84.1%) were classified as having non-severe dengue, of which 70 (48.3%) were classified as having dengue fever (DF), 39 (26.9%) as having dengue hemorrhagic fever (DHF) grade I, and 13 (9%) as having DHF grade II. Twenty-three (15.9%) were classified as having severe dengue, of which 16 (11%) were classified as having DHF grade III and 7 (4.8%) as having DHF grade IV. With clinical interventions included, 8 cases (6.6%) originally classified as having non-severe dengue infection were reclassified as having severe infection (sensitivity = 74%, specificity = 100%, likelihood ratio (-) = 0.26). Using the new dengue classification system, 117 cases (80.7%) were classified as having non-severe dengue infection, of which 79 (54.5%) were classified as having dengue without warning signs and 38 (26.2%) were classified as having dengue with warning signs, while 28 (19.3%) were classified as having severe dengue infection. Using clinical intervention, 4 cases (3.4%) which were originally classified as having non-severe dengue infection were reclassified as having severe dengue infection (sensitivity = 88%, specificity = 99%, likelihood ratio (+) = 98.88, likelihood ratio (-) = 0.13). Binary logistic regression showed the revised dengue classification system (p = 0.000, Wald:22.446) was better in detecting severe dengue infections than the WHO classification system (p = 0.175, Wald:6.339).

  14. 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. PMID:25761891

  15. 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.

  16. Serologic evidence of dengue infection before onset of epidemic, Bangladesh.

    PubMed

    Hossain, M Anowar; Khatun, Mahmuda; Arjumand, Farzana; Nisaluk, Ananda; Breiman, Robert F

    2003-11-01

    Dengue fever emerged in Bangladesh in 2000. We tested 225 serum samples from febrile patients and 184 blood donors in 1996 and 1997 for dengue antibodies; 55 (24.4% ) febrile patients had dengue antibodies ( 65.5% with secondary infection pattern), compared with one (0.54%) donor (p <0.001), suggesting that dengue transmission was ongoing well before 1996.

  17. 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.

  18. 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

  19. 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

  20. Dengue Virus Infection with Highly Neutralizing Levels of Cross-Reactive Antibodies Causes Acute Lethal Small Intestinal Pathology without a High Level of Viremia in Mice

    PubMed Central

    Watanabe, Satoru; Chan, Kitti Wing Ki; Wang, Jiaqi; Rivino, Laura; Lok, Shee-Mei

    2015-01-01

    ABSTRACT Severe dengue virus (DENV)-associated diseases can occur in patients who have preexisting DENV antibodies (Abs) through antibody-dependent enhancement (ADE) of infection. It is well established that during ADE, DENV-antibody immune complexes (ICs) infect Fcγ receptor-bearing cells and increase the systemic viral burden that can be measured in the blood. For protection against infection with DENV serotypes 1 to 4, strongly neutralizing Abs must be elicited to overcome the effect of ADE. Clinical observations in infants who have maternal DENV Abs or recent phase II/III clinical trials with a leading tetravalent dengue vaccine suggested a lack of correlation between Ab neutralization and in vivo disease prevention. In addressing this gap in knowledge, we found that inoculation of ICs formed with serotype cross-reactive Abs that are more than 98% neutralized in vitro promotes high mortality in AG129 mice even though peak viremia was lower than that in direct virus infection. This suggests that the serum viremia level is not always correlated with disease severity. We further demonstrated that infection with the ICs resulted in increased vascular permeability, specifically in the small intestine, accompanied with increased tissue viral load and cytokine production, which can be suppressed by anti-tumor necrosis factor alpha (anti-TNF-α) Abs. Flow cytometric analysis identified increased infection in CD11bint CD11cint/hi CD103− antigen-presenting cells by IC inoculation, suggesting that these infected cells may be responsible for the increase in TNF-α production and vascular permeability in the small intestine that lead to mortality in mice. Our findings may have important implications for the development of dengue therapeutics. IMPORTANCE We examined the relationship between the neutralizing level of Abs at the time of infection and subsequent disease progression in a mouse model in order to understand why patients who are shown to have a neutralizing

  1. 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

  2. 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. PMID:27375618

  3. 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.

  4. 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.

  5. Autoimmune pathogenesis in dengue virus infection.

    PubMed

    Lin, Chiou-Feng; Wan, Shu-Wen; Cheng, Hsien-Jen; Lei, Huan-Yao; Lin, Yee-Shin

    2006-01-01

    The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) caused by dengue virus (DV) infection remain unresolved. Patients with DHF/DSS are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and hepatomegaly. In addition to the effect of virus load and virus variation, abnormal immune responses of the host after DV infection may also account for the progression of DHF/DSS. Actually, viral autoimmunity is involved in the pathogenesis of numerous viral infections, such as human immunodeficiency virus, human hepatitis C virus, human cytomegalovirus, herpes simplex virus, Epstein- Barr virus, and DV. In this review, we discuss the implications of autoimmunity in dengue pathogenesis. Antibodies directed against DV nonstructural protein 1 (NS1) showed cross-reactivity with human platelets and endothelial cells, which lead to platelet and endothelial cell damage and inflammatory activation. Based on these findings, we hypothesize that anti-DV NS1 is involved in the pathogenesis of DF and DHF/DSS, and this may provide important information in dengue vaccine development.

  6. Capillary leakage in travelers with dengue infection: implications for pathogenesis.

    PubMed

    Meltzer, Eyal; Heyman, Zahava; Bin, Hanna; Schwartz, Eli

    2012-03-01

    Dengue hemorrhagic fever is characterized by the presence of a capillary leak syndrome. Its pathogenesis is presumed to differ from that of classical dengue fever (DF) and to be associated with secondary dengue infection. Returning travelers given a diagnosis of DF were evaluated for capillary leakage with abdominal sonography. Data were compared between travelers with primary/secondary infection defined by epidemiologic and serologic parameters. A total of 12 (34.3%) of 35 patients had sonographic signs of capillary leakage. Most (85%) patients with capillary leakage had classical DF. Capillary leak was diagnosed in 32% of primary dengue cases and in 40% of secondary dengue cases (P = 0.69). The two patients given a diagnosis of dengue hemorrhagic fever had primary infections. The high prevalence of capillary leakage among travelers, most of them with primary exposure to dengue, calls into question the importance of secondary infection in causing capillary leakage in dengue infection.

  7. Encephalitis in the clinical spectrum of dengue infection.

    PubMed

    Varatharaj, Aravinthan

    2010-01-01

    Dengue viral infections are common worldwide. Clinical manifestations form a broad spectrum, and include uncomplicated dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Encephalopathy has been well reported and has classically been thought to result from the multisystem derangement that occurs in severe dengue infection; with liver failure, shock, and coagulopathy causing cerebral insult. However, there is increasing evidence for dengue viral neurotropism, suggesting that, in a proportion of cases, there may be an element of direct viral encephalitis. Understanding the pathophysiology of dengue encephalopathy is crucial toward developing a more effective management strategy. This review provides an overview of the clinical spectrum of dengue infection, and examines evidence supporting the existence of dengue encephalitis.

  8. Fulminant hepatitis in dengue infection.

    PubMed

    Lum, L C; Lam, S K; George, R; Devi, S

    1993-09-01

    Eight cases of liver failure and encephalopathy were observed among twenty cases of grade 3 and grade 4 dengue hemorrhagic fever/dengue shock syndrome admitted to the Department of Pediatrics, University Hospital, Kuala Lumpur from January 1990 to December 1991. All patients with deterioriation in mental status showed a marked increase in liver enzymes (aspartate and alanine aminotransaminases) and severe coagulopathy. Six patients needed cerebral protection, including ventilation, intravenous sedation and muscle relaxants. There was one death during the period of study and one case of residual hemiparesis in a boy who had, in addition, intracerebral hemorrhage. All other survivors had complete recovery of liver and neurological function.

  9. Dengue infection in Dhaka City, Bangladesh.

    PubMed

    Sharmin, R; Tabassum, S; Mamun, K Z; Nessa, A; Jahan, M

    2013-10-01

    Dengue fever (DF) and dengue haemorrhagic fever (DHF) are now endemic in Bangladesh with outbreaks being reported quite frequently. This cross sectional study was done clinically suspected dengue patients were selected from different hospitals of Dhaka city, Bangladesh, from January 2008 to December 2008. The clinical features, risk factors and laboratory findings associated with dengue infection were investigated among 201 clinically suspected patients. Antibodies were detected in 137(68.2%) cases. Of these, 80(58.4%) were primary and 57(41.6%) as secondary dengue cases according to presence of dengue-specific IgM and/or IgG antibodies. Among primary cases, 70(87.5%) were DF and 10(12.5%) were DHF cases, in contrast to secondary cases, where 10(18.1%) were DF and 47(81.9%) were DHF cases. Majority (57.9%) of patients presented with Grade I and 42.1% had Grade II disease. Patients between 16-30 years were the most vulnerable age group (81.3% DF and 71.9% DHF patients). Males out-numbered females with 72.5% male vs. 27.5% female patients having DF and 68.4% male vs. 31.6% female patients having DHF. The monsoon period was the peak season for dengue infection. Headache and arthralgia were the most frequent symptoms in both DF and DHF, but vomiting was more common in DHF. The Tourniquet test was significantly positive among DHF than DF cases (p = 0.001). Platelet count was the only laboratory parameter that showed significantly higher values among DHF than DF cases (p = 0.001).

  10. 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

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

    PubMed

    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

    2015-12-11

    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.

  12. Cellular immunology of sequential dengue virus infection and its role in disease pathogenesis.

    PubMed

    Rothman, Alan L

    2010-01-01

    The increased risk for severe dengue disease during secondary dengue virus (DENV) infections, along with the clinical and pathological evidence pointing to cytokines as the proximal mediators of disease, has interested cellular immunologists in exploring the role of DENV-specific T lymphocytes in the pathogenesis of dengue-associated plasma leakage. Recent technological advances in the analysis of virus-specific T cells, applied to blood samples collected before, during and after acute DENV infections, have demonstrated that memory DENV-specific T cells from a prior infection respond with altered cytokine production to heterologous DENV serotypes and that the level of activation and expansion of these memory cells during acute DENV infection correlates with disease severity. Limited data suggest that specific T cell response profiles may predict a higher risk for severe disease during secondary infection. Application of these techniques and principles to animal models and to clinical trials may advance the development of novel therapeutics and protective vaccines. PMID:19802580

  13. Increased activity of indoleamine 2,3-dioxygenase in serum from acutely infected dengue patients linked to gamma interferon antiviral function

    PubMed Central

    Becerra, Aniuska; Warke, Rajas V.; Xhaja, Kris; Evans, Barbara; Evans, James; Martin, Katherine; de Bosch, Norma; Rothman, Alan L.; Bosch, Irene

    2009-01-01

    The depletion of l-tryptophan (L-Trp) has been associated with the inhibition of growth of micro-organisms and also has profound effects on T cell proliferation and immune tolerance. The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses the rate-limiting step in the catabolic pathway of L-Trp. Gene expression analysis has shown upregulation of genes involved in L-Trp catabolism in in vitro models of dengue virus (DENV) infection. To understand the role of IDO during DENV infection, we measured IDO activity in sera from control and DENV-infected patients. We found increased IDO activity, lower levels of L-Trp and higher levels of l-kynurenine in sera from DENV-infected patients during the febrile days of the disease compared with patients with other febrile illnesses and healthy donors. Furthermore, we confirmed upregulation of IDO mRNA expression in response to DENV infection in vitro, using a dendritic cell (DC) model of DENV infection. We found that the antiviral effect of gamma interferon (IFN-γ) in DENV-infected DCs in vitro was partially dependent on IDO activity. Our results demonstrate that IDO plays an important role in the antiviral effect of IFN-γ against DENV infection in vitro and suggest that it has a role in the immune response to DENV infections in vivo. PMID:19264674

  14. A prospective cohort study of dengue infection in schoolchildren in Long Xuyen, Viet Nam.

    PubMed

    Tien, Nguyen Thi Kim; Luxemburger, Christine; Toan, Nguyen Trong; Pollissard-Gadroy, Laurence; Huong, Vu Thi Que; Van Be, Pham; Rang, Nguyen Ngoc; Wartel, Tram-Anh; Lang, Jean

    2010-09-01

    A dynamic school-based cohort of 2-15 year-olds was established in Long Xuyen, Viet Nam to provide epidemiological data for a dengue vaccine efficacy trial. Active surveillance of febrile episodes identified clinically-suspected dengue and acute and convalescent sera were collected. IgG seroconversion between annual seroprevalence surveys identified sub-clinical infections. In 2004, 2190 children were enrolled with 3239, 3146, and 3081 present each year from 2005 to 2007 consecutively. In all, 627 children had a total of 690 clinically-suspected dengue episodes (394 hospitalisations, 296 outpatients) with 284-310 (41.2-45.0%) laboratory-confirmed depending on testing. Dengue serotype 2 was predominant in 2004 and 2005, and serotype 1 in 2006 and 2007. The acute dengue disease incidence rate per 1000 person-years ranged from 16.9 in 2005 to 40.4 in 2007. The average annual incidence of primary dengue infection (IgG seroconversion in previously naïve children) was 11.4% and the symptomatic to asymptomatic primary infection ratio ranged from 1:3-1:6. Study withdrawal rate, a feasibility indicator for conducting efficacy trials, was low: 4.2% per year when excluding children who changed schools. Our 2004-2007 results confirm the high transmission of dengue in children in Long Xuyen and demonstrate the suitability of this study site for a large scale efficacy trial.

  15. 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

  16. Dengue.

    PubMed

    Halstead, Scott B

    2007-11-10

    The four dengue viruses are transmitted in tropical countries that circle the globe. All can cause syndromes that are self-limited or severe. The common severe syndrome--dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS)--is characterised by sudden vascular permeability generated by cytokines released when T cells attack dengue-infected cells. Dengue 1 virus became prevalent in Hawaii where it was transmitted by Aedes albopictus, producing a classic virgin soil epidemic, with clinical disease seen largely in adults. In Cuba and Singapore, sequential dengue infections at long intervals produced unusually severe disease in adults. Evidence suggests that enhancing and cross-reactive neutralising antibodies regulate dengue epidemics and disease severity. Classic DHF/DSS arises during initial dengue infections in infants with low circulating amounts of maternal dengue antibodies, an observation that precludes an exclusive causal role for secondary T-cell responses. Here, I review and discuss data on clinical diagnosis and pathophysiology of vascular permeability and coagulopathy, parenteral treatment of DHF/DSS, and new laboratory tests.

  17. Unusual neurologic manifestations occurring during dengue fever infection.

    PubMed

    Patey, O; Ollivaud, L; Breuil, J; Lafaix, C

    1993-06-01

    This is a report on dengue fever in two young patients in France that were infected in New Caledonia and Thailand. Both presented with unusual neurologic manifestations. The first patient developed a focal subarachnoid hemorrhage that was associated with transient thrombocytopenia. No neurologic vascular malformation was detected; a mild dengue hemorrhagic fever after a previous dengue infection was suspected. The second patient showed peripheral facial palsy one week after apyrexia without any other etiology except the dengue infection. This case was probably a postinfectious syndrome associated with dengue virus. Both patients recovered spontaneously. The circumstances of the neurologic manifestations in these patients may be attributed to the dengue fever virus. However, although neurologic complications reported for dengue fever are unusual, it is reasonable to consider these manifestations as being due to immunopathologic consequences.

  18. A Cluster of Transverse Myelitis Following Dengue Virus Infection in the Brazilian Amazon Region

    PubMed Central

    de Sousa, Adriano Miranda; Alvarenga, Marina Papais; Alvarenga, Regina Maria Papais

    2014-01-01

    Background and Purpose: During the last two decades, clinical reports have begun to place increasing emphasis on the possible neurological complications related to dengue. However, reports of cases with myelitis post dengue are rare. This study describes an unprecedented cluster of transverse myelitis following a dengue virus infection. Methods: 51 possible cases of neurological complications related to dengue were identified by the epidemiological surveillance of the State of Rondônia, Brazil and submitted to serial neurological examination, electromyography, vertebral MR and laboratory investigation to confirm the dengue diagnosis and rule out other arboviruses. Results: The diagnosis of acute transverse myelitis post-dengue was established in 26 patients, the majority were women, young and white. Antibodies against virus IgM were present in all cases and DEN 3 virus was isolated by PCR in one patient. Treatment with IV steroids was useful. Conclusions: The cluster of transverse myelitis post-dengue with favorable clinical outcome here reported suggests an immune mediated mechanism for the spinal cord involvement. Whereas dengue epidemics are frequent in tropical and subtropical countries, the dengue fever should be part in the differential diagnosis of the infectious and post-infectious myelitis. PMID:25324689

  19. Implications of previous subclinical dengue infection but not virus load in dengue hemorrhagic fever.

    PubMed

    Yeh, Wen-Ting; Chen, Rong-Fu; Wang, Lin; Liu, Jien-Wei; Shaio, Men-Fang; Yang, Kuender D

    2006-10-01

    In a study comparing the virus load and immune reaction between patients with primary and secondary dengue-2 (DEN-2) infections in a hospital-based analysis, we found that 40.7% (55/135) of the 135 patients had secondary DEN-2 infection following a DEN-2 outbreak in southern Taiwan. Most of the secondary infections had subclinical primary dengue infections (78.2%; 43/55). Patients with secondary DEN-2 infections had lower platelet counts, and blood interferon-alpha and virus load, but significantly higher interleukin-10 (P=0.030) and anti-DEN-1 neutralization titers (P=0.013) than those with primary infection. Patients with secondary DEN-2 infection also had a higher rate of dengue hemorrhagic fever (DHF) (61.7% vs. 36.3%). A previous subclinical dengue infection is involved in the secondary DEN-2 infection associated with altered immune reaction and higher DHF rate, but lower blood virus load.

  20. Characterization of dengue virus serotype 4 infection in Jakarta, Indonesia.

    PubMed

    Dewi, Beti Ernawati; Naiggolan, Leonard; Putri, Dwi Hilda; Rachmayanti, Novia; Albar, Sarah; Indriastuti, Nadia Tita; Sjamsuridzal, Wellyzar; Sudiro, T Mirawati

    2014-01-01

    Dengue hemorrhagic fever has become a worldwide health issue. Heterologous infection by different serotypes may lead to severe forms of dengue infection and even death. In a cohort study in Jakarta from 2009 to 2010 with inclusion criteria of adults with fever of less than 48 hours, 72% were confirmed dengue infection from a total of suspected 190 dengue patients. Using RT-PCR, 16 patients were infected with DENV-4 with or without co-infection with other serotype(s). Dengue fever (DF) patients (73%) were infected with DENV-4 alone, while mixed infections were present in more severe clinical manifestations of DHF grade I and II. The nucleotide sequences of envelope (E) protein gene of 3 isolates of DENV-4 showed that they belonged to genotype II. There were 50 nucleotide substitutions, but only 3 amino acid changes were found at positions 130, 233 and 455, present in E protein isolated from DHF grade II patient.

  1. A prospective study of dengue infections in Bangkok.

    PubMed

    Burke, D S; Nisalak, A; Johnson, D E; Scott, R M

    1988-01-01

    Dengue infections were prospectively studied among 4- to 16-year-old students at a Bangkok school. Blood samples were obtained from 1,757 students in June 1980, before the dengue season, and in January 1981, after the season, and tested for dengue antibodies by the hemagglutination inhibition method. Classrooms were monitored daily for school absences. Fifty percent of the children had antibodies to, and were presumably immune to, at least 1 dengue serotype by the age of 7 years. Most (90/103, 87%) students who became infected by dengue viruses during the study period were either asymptomatic or minimally symptomatic (absent only 1 day). Most (7/13, 53%) of the symptomatic dengue infections (absent with fever for greater than or equal to 2 days) were clinically recognized as cases of dengue hemorrhagic fever which required hospitalization. None of 47 primary dengue infections required hospitalization, whereas 7 of 56 secondary infections did (P = 0.012). Preexistent dengue immunity, as detected by conventional serologic techniques, was a significant (odds ratio greater than or equal to 6.5) risk factor for development of dengue hemorrhagic fever.

  2. Infection risk to travelers going to dengue fever endemic regions.

    PubMed

    Pongsumpun, P; Patanarapelert, K; Sriprom, M; Varamit, S; Tang, I M

    2004-03-01

    The risk of dengue virus infection to travelers visiting dengue fever endemic regions was studied through the use of mathematical modeling. A Susceptible-Infected-Recovered (SIR) model is used to describe the transmission of dengue fever (DF) in an endemic region into which tourists enter. The dynamics of a new class of human, the traveler, is incorporated into the systems of first order differential equations in the SIR describing the dynamics of the transmission in the host region. Using standard dynamic analysis methods, the numbers of travelers who become infected with the dengue virus are calculated as a function of the length of time the tourist stays in the region.

  3. 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.

  4. 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

  5. Involvement of the central nervous system in patients with dengue virus infection.

    PubMed

    Domingues, Renan B; Kuster, Gustavo W; Onuki-Castro, Fábio L; Souza, Vanda A; Levi, José E; Pannuti, Cláudio S

    2008-04-15

    The findings of a neurological evaluation in 85 patients with confirmed, acute, dengue virus infection are described. Signs of central nervous system involvement were present in 18 patients (21.2%). The most frequent neurological symptom was mental confusion. The frequency of neurological involvement did not differ between patients with primary and secondary dengue infection, and the prevalence of central nervous system involvement in dengue fever and dengue hemorrhagic fever also did not differ significantly. The presence of CNS involvement did not influence the prognosis of dengue infection. Dengue viral CSF RNA was found in 7 of 13 patients submitted to a spinal tap, the CSF viral load being less than 1000 copies/ml. PCR was negative in serum samples obtained from three patients on the same day as the CSF samples, suggesting that the dengue virus actively enters the CNS and that the presence of the virus in the CNS does not result from passive crossing of the blood-brain barrier.

  6. Coincidence of acute brucella hepatitis and dengue fever or serologic cross-reactivity?

    PubMed

    Bzeizi, Khalid I; Benmousa, Ali; Sanai, Faisal M

    2010-01-01

    Hepatic involvement in brucellosis is not uncommon since 10-20% of patient infected with brucella species can have abnormal liver function tests. The usual presentation of brucella hepatitis is in the form of chronic granulomatous hepatitis with mild to moderate elevation of liver enzymes, while acute hepatitis is rare. We report a young patient who presented with acute brucella-induced hepatitis and co-infection with dengue hemorrhagic virus resulting in severe elevation of liver enzymes and absence of granuloma on histology. His mother also simultaneously tested positive for both infections. The patient responded well to anti-brucella therapy with normalization of his liver profile. We discuss, herein, the hepatic involvement of these two infections and discuss the possible serological cross-reactivity between brucella and dengue fever virus.

  7. Dengue-2 virus infection of human mononuclear cell lines and establishment of persistent infections.

    PubMed

    Kurane, I; Kontny, U; Janus, J; Ennis, F A

    1990-01-01

    Twenty three human mononuclear cell lines including ten myelomonocytic cell lines, eight B cell lines and five T cell lines, were examined to determine whether they could be infected with dengue-2 virus. All the cell lines were infected with dengue-2 virus as determined by immunofluorescent staining and by virus titration of culture supernatant fluids. K562, Jiyoye and Jurkat, respectively, showed the highest percentage of infected cells of these myelomonocytic, B and T cell lines. Antibody to dengue-2 virus at subneutralizing concentrations augmented dengue-2 virus infection of myelomonocytic cell lines, but not of B cell lines or of T cell lines. Persistent dengue-2 virus infection was established using a myelomonocytic cell line (K562), a B cell line (Raji), and a T cell line (HSB-2). These cell lines maintained a high percentage (more than 70%) of dengue-2 virus antigen-positive cells for at least 25 weeks. Very low titers of infectious dengue-2 virus were detected in the culture supernatant fluids of the persistently infected cells. Dengue-2 virus antigen-positive Raji cell clones were established from persistently-infected Raji cells using limiting dilutions and all of the cells in these clones were dengue-2 virus antigen-positive. These findings demonstrate that a variety of human mononuclear cell lines can be infected with dengue-2 virus and may be useful as models for the analysis of dengue virus-human cell interactions in dengue virus infections.

  8. Vertical dengue infection: case reports and review.

    PubMed

    Sirinavin, Sayomporn; Nuntnarumit, Pracha; Supapannachart, Sarayuth; Boonkasidecha, Suppawat; Techasaensiri, Chonnamet; Yoksarn, Sutee

    2004-11-01

    Two vertical dengue infection cases are presented, and 15 others are reviewed. Twelve mothers had fever 0-9 (median, 2) days antepartum. The fevers of 17 neonates occurred at 1-11 (median, 4) days of life and lasted for 1-5 (median, 3) days. Neonatal thrombocytopenia was detected at 1-11 (median, 6) days of life and lasted for 3-18 (median, 6) days; the lowest platelet counts were 5-75 x 10(3) (median, 19 x 10 (3))/mm3. One neonate died.

  9. Unsuspected Dengue and Acute Febrile Illness in Rural and Semi-Urban Southern Sri Lanka

    PubMed Central

    Bodinayake, Champika; Nagahawatte, Ajith; Devasiri, Vasantha; Kodikara-Arachichi, Wasantha; Strouse, John J.; Broadwater, Anne; Østbye, Truls; de Silva, Aravinda; Woods, Christopher W.

    2012-01-01

    Dengue virus (DENV), a globally emerging cause of undifferentiated fever, has been documented in the heavily urbanized western coast of Sri Lanka since the 1960s. New areas of Sri Lanka are now being affected, and the reported number and severity of cases have increased. To study emerging DENV in southern Sri Lanka, we obtained epidemiologic and clinical data and acute- and convalescent-phase serum samples from patients >2 years old with febrile illness. We tested paired serum samples for DENV IgG and IgM and serotyped virus by using isolation and reverse transcription PCR. We identified acute DENV infection (serotypes 2, 3, and 4) in 54 (6.3%) of 859 patients. Only 14% of patients had clinically suspected dengue; however, 54% had serologically confirmed acute or past DENV infection. DENV is a major and largely unrecognized cause of fever in southern Sri Lanka, especially in young adults. PMID:22304972

  10. Unsuspected dengue and acute febrile illness in rural and semi-urban southern Sri Lanka.

    PubMed

    Reller, Megan E; Bodinayake, Champika; Nagahawatte, Ajith; Devasiri, Vasantha; Kodikara-Arachichi, Wasantha; Strouse, John J; Broadwater, Anne; Østbye, Truls; de Silva, Aravinda; Woods, Christopher W

    2012-02-01

    Dengue virus (DENV), a globally emerging cause of undifferentiated fever, has been documented in the heavily urbanized western coast of Sri Lanka since the 1960s. New areas of Sri Lanka are now being affected, and the reported number and severity of cases have increased. To study emerging DENV in southern Sri Lanka, we obtained epidemiologic and clinical data and acute- and convalescent-phase serum samples from patients >2 years old with febrile illness. We tested paired serum samples for DENV IgG and IgM and serotyped virus by using isolation and reverse transcription PCR. We identified acute DENV infection (serotypes 2, 3, and 4) in 54 (6.3%) of 859 patients. Only 14% of patients had clinically suspected dengue; however, 54% had serologically confirmed acute or past DENV infection. DENV is a major and largely unrecognized cause of fever in southern Sri Lanka, especially in young adults.

  11. The Clinical, Serological and Molecular Diagnosis of Emerging Dengue Infection at a Tertiary Care Institute in Southern, India

    PubMed Central

    Neeraja, Mamidi; Lakshmi, Vemu; Dash, P.K.; Parida, M.M.; Rao, P.V.L.

    2013-01-01

    Introduction: Dengue is an acute viral infection which presents as uneventful pyrexia to a fatal complication. This infection is increasingly being recognized as the world’s major emerging tropical disease and an important public health problem. This article highlights the clinical manifestations of Dengue virus infection and the various molecular tests that were used for its laboratory diagnosis. Methods: Serum samples from 713 suspected cases of Dengue were collected between August and December 2007. The clinical profiles of 123 hospitalized patients were analyzed. Serology, RT- PCR, virus isolation and sequencing were done. Results: The most common clinical symptoms were fever, thrombocytopenia, rash and elevated liver enzymes. The demonstration of the Dengue RNA in 5.16% samples, the detection of Dengue specific IgM antibodies in 18% samples and the isolation of the DENV-4 and the DENV-3 viruses from the clinical samples confirmed this Dengue outbreak. A co -infection with Chikungunya was observed in 2.06% of the cases. The phylogenetic analysis revealed that the Indian Dengue-4 isolates from this outbreak belonged to the genotype I. This study clearly indicated the sudden dominance of DENV-4 in an Indian Dengue outbreak. Conclusion: The surveillance of the Dengue viruses needs to be closely monitored for the emergence of newer serotype(s) in hitherto unknown areas. PMID:23634396

  12. Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus infections.

    PubMed

    Mairuhu, Albert T A; Peri, Giuseppe; Setiati, Tatty E; Hack, C Erik; Koraka, Penelopie; Soemantri, Augustinus; Osterhaus, Albert D M E; Brandjes, Dees P M; van der Meer, Jos W M; Mantovani, Alberto; van Gorp, Eric C M

    2005-08-01

    C-reactive protein is one of the most widely used indicators of the response of acute-phase proteins. The measurement of C-reactive protein in dengue, however, is clinically not useful, because of marginally elevated levels and absent association with disease severity. The prototypic long pentraxin, pentraxin 3, is an acute phase protein that is structurally related but distinct from C-reactive protein which has proven to correlate with the severity of bacterial infection in critically ill patients. The potential involvement of pentraxin 3 in dengue and its aptitude to predict more severe disease or poor clinical outcome has not been studied previously. We therefore measured pentraxin 3 plasma levels in 44 dengue virus infected patients. Pentraxin 3 levels were strikingly higher when compared to C-reactive protein levels, with highest pentraxin 3 values observed in the first 7 days after the onset of symptoms. Median pentraxin 3 levels at admission and peak levels during follow up were higher in patients suffering from dengue shock syndrome (at admission: 119.3 ng/ml [interquartile range 61.8--188.7], peak values during follow up: 147.9 ng/ml [interquartile range 85.7--204.3]) compared to levels found in patients with dengue fever and dengue hemorrhagic fever (at admission: 59.0 ng/ml [interquartile range 28.6--100.3], P=0.040; peak values during follow up: 80.8 ng/ml [interquartile range 36.1--168.1], P=0.020). Our results indicate that pentraxin 3 seems to be a marker of infection better than C-reactive protein in dengue. The role of pentraxin 3 in the pathogenesis of dengue and its potential as an early prognostic indicator of disease severity needs further assessment.

  13. 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

  14. 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.

  15. Virus isolation for diagnosing dengue virus infections in returning travelers.

    PubMed

    Teichmann, D; Göbels, K; Niedrig, M; Sim-Brandenburg, J-W; Làge-Stehr, J; Grobusch, M P

    2003-11-01

    Dengue fever is recognized as one of the most frequent imported acute febrile illnesses affecting European tourists returning from the tropics. In order to assess the value of virus isolation for the diagnosis of dengue fever, 70 cases of dengue fever confirmed in German travelers during the period 1993-2001 were analyzed retrospectively. In 26 patients who had developed acute febrile illness within 2 weeks following their return from a trip to a dengue-endemic area, 9 of 13 attempts to isolate the virus were successful in sera drawn 1-5 days and 2 of 13 sera drawn 6-10 days after the onset of illness. DEN-1 was the most frequent serotype isolated. If performed early, virus isolation is a reliable tool for detecting dengue virus in returning travelers.

  16. Analysis of repeat hospital admissions for dengue to estimate the frequency of third or fourth dengue infections resulting in admissions and dengue hemorrhagic fever, and serotype sequences.

    PubMed

    Gibbons, Robert V; Kalanarooj, Siripen; Jarman, Richard G; Nisalak, Ananda; Vaughn, David W; Endy, Timothy P; Mammen, Mammen P; Srikiatkhachorn, Anon

    2007-11-01

    Immunity to a single dengue virus (DENV) infection does not provide heterologous immunity to subsequent infection. In fact, the greatest risk for dengue hemorrhagic fever (DHF) is with a second DENV serotype exposure. The risk for DHF with a third or fourth dengue infection relative to a first or second exposure is not known. An analysis of our database of children admitted to the Queen Sirikit National Institute of Child Health and Kamphaeng Phet Provincial Hospital with suspected dengue illness revealed that the number of dengue admissions caused by a third or fourth DENV infection was extremely low (0.08-0.8%). Once admitted, the risk for DHF relative to dengue fever was not different for those experiencing third or fourth DENV infections over those experiencing a second DENV infection. We document new dengue serotype infection sequences leading to DHF of 1-4, 2-3, 3-1, and 3-4.

  17. Novel evidence of microglial immune response in impairment of Dengue infection of CNS.

    PubMed

    Bhatt, Rushil S; Kothari, Sweta T; Gohil, Devanshi J; D'Souza, Marsha; Chowdhary, Abhay S

    2015-10-01

    Dengue, the most rampant zoonotic viral disease in tropics, contributes to 14% of acute febrile illness cases globally. Encephalitis in primary Dengue fever, with/without haemorrhage has been reported occasionally. Our study presents novel evidence for this rarity at the molecular level. Murine microglia (BV2) were infected in-vitro with Dengue virus (DENV) serotypes (1-4) and their immune response was evaluated. Gene expressions of TNF-α, IL-10, IFN-γ, and IL1-β constituted the pro-inflammatory response, levels of MCP-1 and IL-6 represented the regulatory mechanism and changes in the levels of Occludin, MMP-2, MMP-9 and TIMP-1 encompassed the break-down of the blood-brain barrier (BBB). Cytokine response was studied using RT-PCR, with relative fold change assessed using ΔΔCt method. We observed that DENV1 increased vascular permeability and trans-membrane transport, while DENV2 resulted in oxidative stress. DENV3 infection presented with impaired immune response and DENV4 manifested a chaotropic response of the BBB protein genes. However, no serotype was able to breakdown the BBB, thus validating the low prevalence of encephalitis in dengue. Our study is the first reported evidence of the microglial immune response resisting the entry of DENV into the CNS. It also supports the theory that primary Dengue infection results in the acute inflammation of the microglia, and the host immune response plays a critical role in development of encephalitis.

  18. Seropositivity and pattern of dengue infection in Dhaka city.

    PubMed

    Rahman, M T; Tahmin, H A; Mannan, T; Sultana, R

    2007-07-01

    Bangladesh is experiencing resurgence of' dengue endemic since 2000. In an attempt to see the pattern of' dengue infection we analyzed retrospectively results of 225 blood samples from patients having fever and clinically suspected to have been suffering from dengue fever who were tested for dengue IgM and IgG in Health Care Development Project (HCDP), Dhaka, an enterprise of Diabetic Association of Bangladesh (DAB) one of the largest private health care facility provider in Bangladesh. Out of 225 samples tested, a total of 156(69.33%) cases were serologically positive for dengue and 69(30.67%) were negative. Of the positive cases, 70(44.87%) were positive for Dengue IgM and 86(55.13%) were positive for Dengue IgG. which showed statistical difference between male and female (p<0.05). Both IgM and IgG, were positive in 23(14, 74%) cases. The mean age +/-SD of affected is 36.86+/-17.60 years and the maximum number of positive cases 114(73.08%) diagnosed were in the months between July-December. It is evident from the present study that dengue is endemic in Dhaka city particularly during monsoon and rainy season. Secondary dengue is more common than primary dengue and both preventive and curative measures are needed to combat this menace.

  19. 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. PMID:17356302

  20. Dengue specific immunoglobulins M, A, and E in primary and secondary dengue 4 infected Salvadorian children.

    PubMed

    Vazquez, Susana; Lozano, Celina; Perez, Ana Beatriz; Castellanos, Yinet; Ruiz, Didye; Calzada, Naifi; Guzmán, Maria Guadalupe

    2014-09-01

    El Salvador is a Central American country that has been affected by several dengue outbreaks. This study investigated the levels of IgM, IgA, and IgE anti-dengue antibodies in serum samples from children in El Salvador, with a clinical and serological diagnosis of dengue infection during the dengue 4 outbreak in 2002-2003. Seventy one serum samples were tested by ELISA and cases were classified in three groups: 13 primary dengue fever (PDF), 21 secondary dengue fever (SDF), and 37 secondary dengue hemorrhagic fever (SDHF). Also, the specificity of anti-dengue IgM for the different serotypes was tested. No significant differences in the IgM response were found between PDF and SDF, but these were detected between PDF and SDHF (P = 0.0053) and between SDF and SDHF (P = 0.0003). The IgA and IgE values showed a statistically significant difference between primary and secondary groups. The highest positivity percentage of IgA was between 95% (SDF) and 100% (SDHF) towards day 7 of onset of fever. All secondary cases were positive for IgE antibodies. The specificity of IgM was determined for DENV-4 virus in primary and secondary DF groups. This is the first study on dengue cases in Salvadorian children related to the immune response of different immunoglobulins to the type of infection and the clinical picture. Further prospective studies are needed to define if the pattern of immunoglobulins can determine early dengue infection and/or severity.

  1. 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

  2. Epidemiological features of dengue and chikungunya infections in Burma.

    PubMed

    Thaung, U; Ming, C K; Swe, T; Thein, S

    1975-06-01

    A serological survey for antibody to dengue and chikungunya was carried out in all 14 divisions and states and 2 border towns in Burma during 1973-74. Dengue HI antibody prevalence rate of less than 10% was observed in Arakan and Shan States, 10 to 30% in the Irrawaddy, Pegu, Mandalay Divisions and Kachin, Mon and Karen States, 31 to 60% in Sagaing Division, and over 60% in Rangoon, Magwe and Tenasserim Divisions. Similarly, chikungunya HI antibody prevalence rate of less than 10% was observed in Arakan State, 10 to 30% in the Irrawaddy, Pegu, Mandalay and Sagaing Divisions and Kachin State, 31 to 60% in Rangoon Division and Mon State. Both dengue and chikungunya antibodies were detected where Aedes aegypti mosquitoes were prevalent but the antibody prevalent rates were not directly proportional to the premises index. No HI antibody to dengue nor chikungunya was detected in Aedes aegypti free hilly areas, Chin and Kayah States, but was detected in the Shan State, Dengue and chikungunya infections were observed both in rural and urban populations. Dengue and chikungunya infections affected all socioeconomic classes in Rangoon equally but in Mandalay high socioeconomic class was nearly 3 times less affected than lower socioeconomic class. The infrequencies of dengue and chikungunya infections were observed to be 2 to 3 times higher in residents of Rangoon City than those of other towns. In Rangoon the antibody prevalence rates to dengue increased progressively with age while in other towns no appreciable increase in rates with age was observed. Both sexes were equally affected. This study provides strong circumstantial evidence that dengue and chikungunya viruses are highly and widely distributed throughout Burma, and that new outbreaks of haemorrhagic fever could occur in previously free areas following introduction of dengue viruses into populations previously exposed to one type of dengue.

  3. Viraemia in patients with naturally acquired dengue infection.

    PubMed

    Gubler, D J; Suharyono, W; Tan, R; Abidin, M; Sie, A

    1981-01-01

    The magnitude and duration of dengue viraemia were studied in 153 patients with naturally acquired dengue infection in Jakarta, Indonesia. The duration of viraemia ranged from 2 to 12 days, but most patients had detectable circulating virus for 4-5 days. Accurate measurement of peak virus titres was not possible for many patients because of late admission to the hospital. Composite pictures of viraemia for each serotype, however, showed that many patients infected with dengue 1, 2, or 3 had circulating virus titres ranging from barely detectable to over 10(8) MID(50) per ml for 3-5 days. Virus titres in patients infected with dengue 4 were about 100-fold lower. Dengue haemagglutination-inhibition antibody titres of 80 or less had little effect on viraemia, but antibody titres of 160 or greater were associated with a decrease in virus isolation rate and in virus titre. The duration and magnitude of viraemia did not vary significantly with the severity of the disease and was only slightly higher in patients classified as primary dengue infections than in those classified as secondary infections. Measurement of viraemia in fatal dengue haemorrhagic fever (DHF) cases showed that these patients had significant quantities of circulating virus at the time of death.

  4. Evaluation of Commercially Available Assays for Diagnosis of Acute Dengue in Schoolchildren During an Epidemic Period in Medellin, Colombia.

    PubMed

    Piedrahita, Leidy D; Agudelo, Ivony Y; Trujillo, Andrea I; Ramírez, Ruth E; Osorio, Jorge E; Restrepo, Berta N

    2016-08-01

    During an active surveillance study in school children in Medellin, we assessed the performance of two diagnostic strategies for dengue virus. A total of 41 patients with suspected dengue acute infection were evaluated. Diagnostic strategies consisted of one combining Panbio(®) Dengue virus IgM and IgG Capture ELISAs (enzyme-linked immunosorbent assays) with reverse transcriptase polymerase chain reaction (RT-PCR) and another using a commercial rapid SD Bioline Dengue Duo (IgG/IgM + NS1 Ag) test. These two strategies were compared with the enzyme-linked immunospot microneutralization test (ELISPOT-MNT). The sensitivity and specificity were 53.9% and 80.0% for the combination of Panbio(®) ELISAs and RT-PCR tests, and 30.8% and 73.3% for the SD Bioline Duo test, respectively. ELISPOT-MNT detected 16.4% additional cases and revealed the presence of neutralizing antibodies in all the acute samples, evidencing that they were all secondary infections. In contrast, Panbio(®) and SD Dengue Duo rapid tests only classified 23.0% and 26.9% of the cases as secondary dengue infections, respectively. Cohen's kappa coefficient and McNemar's association tests demonstrated a significant disagreement between the two diagnostic strategies and ELISPOT-MNT. Overall, these results evidence the relatively poor performances of commercial assays for the diagnosis of acute and secondary dengue infections, compared with ELISPOT-MNT, and raise concern about the accuracy of these assays for the diagnostic of dengue in endemic areas. PMID:27185768

  5. Evaluation of Commercially Available Assays for Diagnosis of Acute Dengue in Schoolchildren During an Epidemic Period in Medellin, Colombia.

    PubMed

    Piedrahita, Leidy D; Agudelo, Ivony Y; Trujillo, Andrea I; Ramírez, Ruth E; Osorio, Jorge E; Restrepo, Berta N

    2016-08-01

    During an active surveillance study in school children in Medellin, we assessed the performance of two diagnostic strategies for dengue virus. A total of 41 patients with suspected dengue acute infection were evaluated. Diagnostic strategies consisted of one combining Panbio(®) Dengue virus IgM and IgG Capture ELISAs (enzyme-linked immunosorbent assays) with reverse transcriptase polymerase chain reaction (RT-PCR) and another using a commercial rapid SD Bioline Dengue Duo (IgG/IgM + NS1 Ag) test. These two strategies were compared with the enzyme-linked immunospot microneutralization test (ELISPOT-MNT). The sensitivity and specificity were 53.9% and 80.0% for the combination of Panbio(®) ELISAs and RT-PCR tests, and 30.8% and 73.3% for the SD Bioline Duo test, respectively. ELISPOT-MNT detected 16.4% additional cases and revealed the presence of neutralizing antibodies in all the acute samples, evidencing that they were all secondary infections. In contrast, Panbio(®) and SD Dengue Duo rapid tests only classified 23.0% and 26.9% of the cases as secondary dengue infections, respectively. Cohen's kappa coefficient and McNemar's association tests demonstrated a significant disagreement between the two diagnostic strategies and ELISPOT-MNT. Overall, these results evidence the relatively poor performances of commercial assays for the diagnosis of acute and secondary dengue infections, compared with ELISPOT-MNT, and raise concern about the accuracy of these assays for the diagnostic of dengue in endemic areas.

  6. Ear infection - acute

    MedlinePlus

    ... Risk factors for acute ear infections include: Attending day care (especially centers with more than 6 children) Changes ... hands and toys often. If possible, choose a day care that has 6 or fewer children. This can ...

  7. Influence of the dengue serotype, previous dengue infection, and plasma viral load on clinical presentation and outcome during a dengue-2 and dengue-4 co-epidemic.

    PubMed

    Thomas, Laurent; Verlaeten, Olivier; Cabié, André; Kaidomar, Stéphane; Moravie, Victor; Martial, Jenny; Najioullah, Fatiha; Plumelle, Yves; Fonteau, Christiane; Dussart, Philippe; Césaire, Raymond

    2008-06-01

    Martinique experienced a dengue outbreak with co-circulation of DENV-2 and DENV-4. In an emergency department-based study, we analyzed whether the clinical presentation and outcome of adult patients were related to serotype, immune status, or plasma viral load. Of the 146 adult patients who had confirmed dengue infection, 91 (62.3%) were classified as having classic dengue fever, 11 (7.5%) fulfilled World Health Organization criteria for dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), 21 other patients (14.4%) presented with at least one typical feature of DHF/DSS [i.e., internal hemorrhage, plasma leakage, marked thrombocytopenia (platelet count < or = 50,000 platelets/mm(3)) and/or shock], and 23 further patients (15.8%) had unusual manifestations. Four patients died. Severe illness was more frequent in patients with secondary dengue infection (odds ratio, 7.18; 95% confidence interval, 3.1-16.7; P < 0.001). Multivariate regression analysis showed that gastrointestinal symptoms and other unusual manifestations were independently associated with DENV-2 infection, whereas cough and DHF/DSS features were independently associated with secondary immune response. A high plasma viral load was associated with DENV-2 infection, increased serum liver enzymes, and with DHF/DSS features in patients presenting after the third day of illness. The most severe cases of dengue resulted from the combined effects of DENV-2 and secondary infection.

  8. Frequency and Clinical Features of Dengue Infection in a Schoolchildren Cohort from Medellin, Colombia

    PubMed Central

    Restrepo, Berta Nelly; Piedrahita, Leidy Diana; Agudelo, Ivony Yireth; Parra-Henao, Gabriel; Osorio, Jorge E.

    2012-01-01

    To determine the incidence of dengue infection, we established active surveillance of febrile episodes in a cohort of schoolchildren from three schools in Medellin, Colombia. We followed a cohort of 2,379 schoolchildren in 2010 and followed 1,840 of these children the following year. During the follow-up time, 264 schoolchildren displayed 297 febrile episodes; of these, 23 episodes (7.7%) were caused by acute dengue infection. All four dengue serotypes were found, and all of the cases were mild. The most common symptoms in the dengue cases compared with those in other febrile illness were asthenia (96% versus 87%), anorexia (78% versus 57%), rhinorrhea (65.2% versus 58%), abdominal pain (56.5% versus 47.8%), arthralgia (43% versus 33%), and positive tourniquet test (13% versus 3%). This difference was not statistically significant. Pulse was elevated, and systolic arterial pressure was lower in dengue cases compared with other febrile illness (P < 0.05). Mosquito indexes were determined in 8 children's houses and in the schools. Aedes aegypti adults were found in both households and in schools, whereas Aedes aegypti larvae were found only in schools. These results showed an elevated dengue frequency in children, with symptoms similar to those of other febrile illness and transmission risk in households and schools. PMID:23304167

  9. Serum nitric oxide in children with dengue infection.

    PubMed

    Trairatvorakul, Pon; Chongsrisawat, Voranush; Ngamvasinont, Direk; Asawarachun, Duangporn; Nantasook, Jutarat; Poovorawan, Yong

    2005-01-01

    One hundred and ten patients (M/F = 67/43) from King Chulalongkorn Memorial Hospital and the provincial hospitals of Uttaradit, Ayudhaya, and Sakonnakorn, who were clinically diagnosed with dengue infection and serologically confirmed by ELISA anti-Dengue IgM and IgG were recruited. Their serum NO level was measured using commercially available assay kits to investigate its correlation with the severity of the dengue infection: dengue fever (DF), DHF I/II, and DHF III/IV or dengue shock syndrome (DSS). Serum NO levels were also measured in 38 healthy controls (M/F = 19/19). Serum NO levels in dengue patients were lower than those of the controls (control = 168.18 +/- 24.10 micromol/l, DF = 124.94 +/- 36.79 micromol/l, DHF I/II = 99.69 +/- 33.42 micromol/l, and DHF III/IV = 120.63 +/- 46.26 micromol/l; p < 0.05). Serum NO levels in patients with DHF I/II were significantly lower than in those with DHF III/IV. These preliminary data revealed that levels of serum NO in dengue patients were significantly lower than those of normal controls. Patients with DSS had higher NO levels than those with DHF I/II. The decreased NO in dengue patients could be due to endothelial damage rendering the endothelium incapable of producing NO. Endothelial function seems to play a role in the pathogenesis of dengue infection. Further studies are required to see whether serum NO levels could play a role in the course of the disease and could help predict the severity of dengue infection.

  10. Bleeding and other presentations in Thai patients with dengue infection.

    PubMed

    Wiwanitkit, Viroj

    2004-10-01

    Dengue infection is a major public health problem, affecting the general population in Southeast Asia. Hematologic aberrations in dengue infection include atypical lymphocytosis, coagulopathy, and predominant thrombocytopenia. Bleeding and other presentations in 30 Thai patients with dengue infection during an endemic season (2003) are presented. A review of the clinical presentation of these patients was performed. All had fever as a chief complaint. The three most common complaints were fever (100%), vomiting (90%), and cough (90%), respectively. Concerning bleeding, only eight cases (26.6%) had signs of bleeding. Those manifestations included petechiae (seven cases, 23.3%) and melena (one case, 3.3%). Skin bleeding (petechiae) due to thrombocytopenia is the most common bleeding manifestation in dengue infection. However, physicians should not overlook bleeding from other less common sites such as the gastrointestinal tract and genitourinary tract.

  11. Spatial analysis of notified dengue fever infections.

    PubMed

    Hu, W; Clements, A; Williams, G; Tong, S

    2011-03-01

    This study aimed to investigate the spatial clustering and dynamic dispersion of dengue incidence in Queensland, Australia. We used Moran's I statistic to assess the spatial autocorrelation of reported dengue cases. Spatial empirical Bayes smoothing estimates were used to display the spatial distribution of dengue in postal areas throughout Queensland. Local indicators of spatial association (LISA) maps and logistic regression models were used to identify spatial clusters and examine the spatio-temporal patterns of the spread of dengue. The results indicate that the spatial distribution of dengue was clustered during each of the three periods of 1993-1996, 1997-2000 and 2001-2004. The high-incidence clusters of dengue were primarily concentrated in the north of Queensland and low-incidence clusters occurred in the south-east of Queensland. The study concludes that the geographical range of notified dengue cases has significantly expanded in Queensland over recent years.

  12. ELECTROLYTE DISTURBANCE AND KIDNEY DYSFUNCTION IN DENGUE VIRAL INFECTION.

    PubMed

    Vachvanichsanong, Prayong; McNeil, Edward

    2015-01-01

    Dengue virus infection (DVI) is endemic in tropical countries in both children and adults. The classical presentation includes fever, hepatomegaly, thrombocytopenia-related bleeding disorders, and plasma leakage. Multi-organ involvement, including kidneys is found in complex cases. Asymptomatic electrolyte disturbances, abnormal urinalysis, and more severe manifestation such as acute kidney injury (AKI) usually indicate kidney involvement. Such manifestations are not rare in DVI, but are often not recognized and can cause the physician to misread the real situation of the patient. The prevalence of electrolyte disturbances or kidney involvement reported in studies varies widely by country and mainly depends on the severity of DVI and age of the patients. The prevalence of DVI-induced AKI ranges from 0.2%-10.0% in children and 2.2%-35.7% in adults. The prevalence among all age groups appears to be increasing in the last decade. Dengue shock syndrome (DSS) has been reported to be an independent risk factor for AKI development. The mechanism of DVI-induced AKI is complex and the details are to date undetermined. Urinalysis, serum electrolytes and creatinine measurements should be performed to document renal involvement in DVI patients for early detection and initiation of appropriate fluid therapy with close monitoring. Renal replacement therapy may be required in some cases. The presence of AKI dramatically increases the mortality rate among both childhood and adulthood DVI from 12%-44% to more than 60%.

  13. Acute myocarditis in dengue hemorrhagic fever: a case report and review of cardiac complications in dengue-affected patients.

    PubMed

    Lee, Ing-Kit; Lee, Wen-Huei; Liu, Jien-Wei; Yang, Kuender D

    2010-10-01

    We report a case of dengue hemorrhagic fever (DHF) complicated by acute myocarditis and review the literature. A 65-year-old woman experienced DHF due to dengue virus serotype 3, complicated with acute myocarditis and acute pulmonary edema. Clinically this masqueraded as acute myocardial infarction, with an electrocardiographically depressed ST segment in precordial leads and elevated serum cardiac-specific troponin I level. Under supportive management, the patient recovered 3 days later. A total of 18 pertinent articles involving 339 dengue-affected patients with cardiac complications were found by PubMed search. Clinical manifestations of cardiac complications varied considerably, from self-limiting tachy-brady arrhythmia to severe myocardial damage, leading to hypotension and pulmonary edema. Although rare, a fatal outcome was reported in some cases of dengue with cardiac complications. To avoid otherwise preventable morbidity and mortality, physicians should have a high index of suspicion for cardiac complications in patients with dengue illness and should manage this accordingly.

  14. Mania in dengue fever

    PubMed Central

    Jhanjee, Anurag; Bhatia, M. S.; Srivastava, Shruti

    2011-01-01

    Dengue fever, also known as break bone fever, is a mosquito-borne infection that causes a severe flu-like illness. During the last few years, there had been increasing reports of dengue fever with unusual manifestations, primarily with neurological symptoms. Psychiatric morbidity during acute dengue infection has rarely been reported. There has not been any systemic study mentioning the prevalence and pattern of psychiatric sequelae. We report a 28-year-old male who after an acute dengue infection developed an episode of mania which was successfully treated. PMID:22969182

  15. Dynamics of interleukin-21 production during the clinical course of primary and secondary dengue virus infections.

    PubMed

    Vivanco-Cid, H; Maldonado-Rentería, M J; Sánchez-Vargas, L A; Izaguirre-Hernández, I Y; Hernández-Flores, K G; Remes-Ruiz, R

    2014-09-01

    Previous studies have revealed the clinical relevance of pro-inflammatory cytokine production during dengue virus (DENV) infections. In this study, we evaluated the production of interleukin-21 (IL-21), a key soluble mediator mainly produced by CD4+ T cells. The aim of this study was to investigate the role of IL-21 production during the clinical course of primary and secondary DENV infections and the potential association of IL-21 serum levels with the disease pathogenesis. Blood samples from DENV-infected patients were collected on different days after the onset of symptoms. Patients were classified according to their phase of disease (acute vs. convalescent phases), the type of infection (primary vs. secondary), and the clinical severity of their disease (dengue fever (DF) vs. dengue hemorrhagic fever (DHF)). IL-21 levels were measured using a quantitative capture ELISA assay. The levels of IL-21 were significantly elevated in the disease group compared with the control group. IL-21 was detected in primary and secondary DENV infections, with a significantly higher concentration in the convalescent phase of primary infections. IL-21 levels were significantly higher in patients with secondary acute DHF infections when compared with those with secondary acute DF infection. There was a relationship between the elevated serum levels of IL-21 and the production of DENV-specific IgM and IgG antibodies. Taking together, our results show for the first time the involvement of IL-21 during the clinical course of DENV infections. We speculate that IL-21 may play a protective role in the context of the convalescent phase of primary infections and the acute phase of secondary infections.

  16. The incidence, characteristics, and presentation of dengue virus infections during infancy.

    PubMed

    Capeding, Rosario Z; Brion, Job D; Caponpon, Mercydina M; Gibbons, Robert V; Jarman, Richard G; Yoon, In-Kyu; Libraty, Daniel H

    2010-02-01

    Infants are a vulnerable and unique population at risk for dengue in endemic areas. This report describes the incidence and presenting clinical features of infant dengue virus (DENV) infections from a prospective community-based study performed between January 2007 and May 2009 in the Philippines. DENV3 was the predominant infecting serotype over a wide spectrum of disease severity, ranging from inapparent infection to dengue hemorrhagic fever (DHF). In 2007, the incidence of inapparent DENV infections during infancy was 103 per 1,000 persons person-years and 6-fold higher than symptomatic dengue. The age-specific incidence of infant DHF was 0.5 per 1,000 persons over the age of 3-8 months, and it disappeared by age 9 months. A febrile seizure, macular rash, petechiae, and lower platelet count were presenting clinical features associated with DENV infection among infants with acute undifferentiated febrile illnesses. Community-based studies can help to delineate the incidence rates, disease spectrum, and clinical features of DENV infections during infancy.

  17. The Incidence, Characteristics, and Presentation of Dengue Virus Infections during Infancy

    PubMed Central

    Capeding, Rosario Z.; Brion, Job D.; Caponpon, Mercydina M.; Gibbons, Robert V.; Jarman, Richard G.; Yoon, In-Kyu; Libraty, Daniel H.

    2010-01-01

    Infants are a vulnerable and unique population at risk for dengue in endemic areas. This report describes the incidence and presenting clinical features of infant dengue virus (DENV) infections from a prospective community-based study performed between January 2007 and May 2009 in the Philippines. DENV3 was the predominant infecting serotype over a wide spectrum of disease severity, ranging from inapparent infection to dengue hemorrhagic fever (DHF). In 2007, the incidence of inapparent DENV infections during infancy was 103 per 1,000 persons person-years and 6-fold higher than symptomatic dengue. The age-specific incidence of infant DHF was 0.5 per 1,000 persons over the age of 3–8 months, and it disappeared by age 9 months. A febrile seizure, macular rash, petechiae, and lower platelet count were presenting clinical features associated with DENV infection among infants with acute undifferentiated febrile illnesses. Community-based studies can help to delineate the incidence rates, disease spectrum, and clinical features of DENV infections during infancy. PMID:20134013

  18. 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

  19. Dengue fever causing febrile neutropenia in children with acute lymphoblastic leukemia: an unknown entity.

    PubMed

    Ramzan, Mohammed; Yadav, Satya Prakash; Dinand, Veronique; Sachdeva, Anupam

    2013-06-01

    Dengue fever is endemic in many parts of the world but it has not been described as a cause of febrile neutropenia. We describe here clinical features, laboratory values and outcome in 10 children with acute lymphoblastic leukemia (ALL) and with dengue fever as a cause of febrile neutropenia. These data are compared to an age-matched control population of 22 children with proven dengue infection without ALL. Except for fever in all patients and plethoric face in one patient, typical symptoms of dengue such as abdominal pain, myalgias, and headaches, were absent. Mean duration of hospital stay was 6.3±2.0 days in ALL patients vs. 5.0±2.0 in controls (p=0.096). Median platelet count was 13,000/cmm (range 1000-28,000) in cases vs. 31,500 (range 13,000-150,000) in controls (p=0.018). Mean time for recovery for platelet was 6.0±1.3days in ALL patients vs. 2.5±0.9days in controls (p<0.001). All 10 patients survived. In endemic areas, high suspicion of dengue fever should be maintained in children with ALL and febrile neutropenia although typical symptoms may be lacking. Platelet recovery may be significantly delayed.

  20. 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

  1. Alternate hypothesis on the pathogenesis of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in dengue virus infection.

    PubMed

    Noisakran, Sansanee; Perng, Guey Chuen

    2008-04-01

    Dengue fever, caused by infection with dengue virus, is not a new disease, but recently because of its serious emerging health threats, coupled with possible dire consequences including death, it has aroused considerable medical and public health concerns worldwide. Today, dengue is considered one of the most important arthropod-borne viral diseases in humans in terms of morbidity and mortality. Globally, it is estimated that approximate 50 to 100 million new dengue virus infections occur annually. Among these, there are 200,000 to 500,000 cases of potential life-threatening dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), characterized by thrombocytopenia and increased vascular permeability. The death rate associated with the more severe form DHF/DSS is approximately 5%, predominantly in children under the age of 15. Although intensive efforts have been made to study the early clinical pathophysiology of dengue infection with the objective to identify the potential cause of DHF, results or data that have accumulated from different regions of the world involving studies of different ethnicity groups are inconsistent at present in terms of identifying a unified hypothesis for the pathogenesis of DHF/DSS. Thus, the potential mechanisms involved in the pathogenesis of DHF and DSS remain elusive. The purpose of this review is to identify alternate factors, such as innate immune parameters, hyper-thermal factors, conditioning of neutralizing antibody, concept of vector transmission, and physical status of virus in viremic patients that may play a role in the induction of DHF and DSS, which might have directly or indirectly contributed to the discrepancies that are noted in the literature reported to date. It is the hope that identification of an alternative explanation for the pathogenesis of DHF/DSS will pave the way for the institution of new strategies for the prevention of this complicated disease.

  2. Mortality from septic shock in a dengue infected patient: a case report.

    PubMed

    Tsai, Jih-Jin; Hsieh, Min-Han; Liu, Li-Teh; Hsiao, Hui-Mien; Perng, Guey Chuen

    2013-07-01

    Dengue infection can be associated with secondary infections which may be challenging to recognize due to the overlap with the symptoms of dengue infection. We report here the case of a 48 year old Chinese female with dengue fever with a fatal secondary bacterial infection due to Enterococcus faecium.

  3. Current neurological observations and complications of dengue virus infection.

    PubMed

    Solbrig, Marylou V; Perng, Guey-Chuen

    2015-06-01

    Dengue, a mosquito-borne flavivirus and fastest growing tropical disease in the world, has experienced an explosion of neurologic case reports and series in recent years. Now dengue is a frequent or leading cause of encephalitis in some endemic regions, is estimated to infect one in six tourists returning from the tropics, and has been proven to have local transmission within the continental USA. High documentation of neurologic disease in recent years reflects increases in overall cases, enhanced clinical awareness and advances in diagnostics. Neurological aspects of dengue virus, along with epidemiology, treatment, and vaccine progress, are presented. PMID:25877545

  4. Unusual clinical manifestations of dengue virus infection.

    PubMed

    George, R; Liam, C K; Chua, C T; Lam, S K; Pang, T; Geethan, R; Foo, L S

    1988-12-01

    Four recent cases of dengue fever with severe, unusual clinical manifestations are described. Two of these cases had features of fulminant hepatitis and encephalopathy; one of these cases was fatal. The two remaining cases showed hepatitis with renal impairment. The significance and importance of these unusual manifestations of dengue disease are discussed.

  5. A preliminary study of dengue infection in Brunei.

    PubMed

    Osman, Osmali; Fong, Mun Yik; Devi, Shamala

    2007-07-01

    The purpose of this study was to examine the extent of dengue infection in Brunei and to determine the predominant serotype circulating in the country. The study generated useful epidemiological data on dengue infection in Brunei. A total of 271 samples from patients suspected of having dengue infections were selected and analyzed. All patients were seen in clinics and hospitals in Brunei. The samples were collected from April 2005 to April 2006 and transported to the WHO Collaborating Centre for Arbovirus Reference and Research, University of Malaya, Malaysia. The following tests were used to achieve the objectives: in-house IgM-capture enzyme-linked immunosorbent assay, virus isolation in mosquito albopictus cell line (C6/36), and viral RNA detection and serotyping by reverse transcriptase-polymerase chain reaction (RT-PCR). The results show that 45 people were positive for dengue-specific IgM (27 males and 18 females), while RT-PCR detected dengue viral RNA in 12 patients, 3 identified as DEN-1 and 9 as DEN-2. Dengue virus was isolated from 6 patients using the C6/36 cell line; 3 were DEN-2 isolates and 3 were DEN-1 isolates. These data show that dengue virus is circulating in Brunei and the predominant infecting serotype for that period was DEN-2 followed by DEN-1. This study is the first to report the detection and isolation of dengue virus from Brunei using RT-PCR and culture in the C6/36 albopictus mosquito cell line.

  6. Impact of dengue virus infection and its control.

    PubMed

    Igarashi, A

    1997-08-01

    Dengue virus infection has been counted among emerging and re-emerging diseases because of (1) the increasing number of patients, (2) the expansion of epidemic areas, and (3) the appearance of severe clinical manifestation of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), which is often fatal if not properly treated. In the meantime, there are no effective dengue control measures: a dengue vaccine is still under development and vector control does not provide a long-lasting effect. In order to obtain direct evidence for the virulent virus theory concerning the pathogenesis of DHF/DSS, type 2 dengue virus strains isolated from patients with different clinical severities in the same epidemic area in northeast Thailand, during the same season, were comparatively sequenced. The result revealed a DF strain specific amino acid substitution from I to R in the PrM, and a DSS strain specific amino acid substitution from D to G in the NS1 gene regions, which could significantly alter the nature of these proteins. Moreover, DF strain specific nucleotide substitutions in the 3' noncoding region were predicted to alter its secondary structure. These amino acid and nucleotide substitutions in other strains isolated in different epidemic areas during other seasons, together with their biological significance, remain to be confirmed. In order to innovate dengue vector control, field tests were carried out in dengue epidemic areas in Vietnam to examine the efficacy of Olyset Net screen, which is a wide-mesh net made of polyethylene thread impregnated with permethrin. The results show that Olyset Net (1) reduced the number of principal dengue vector species, Aedes aegypti, (2) interrupted the silent transmission of dengue viruses and (3) was highly appreciated by the local people as a convenient and comfortable vector control method. This encouraging evaluation of the Olyset Net screen should be confirmed further by other tests under different settings.

  7. Clinical and laboratory profile of dengue infection in children.

    PubMed

    Shah, G S; Islam, S; Das, B K

    2006-01-01

    The present work is a prospective, observational, hospital based study on 100 sero positive cases of dengue infection, admitted to Dhaka Children Hospital, Dhaka, Bangladesh during the period 2000 -2001. The patients were in the age group 8 months to 14 years with a mean age of 8.3 years. The serological tests were performed by rapid strip test. Primary dengue infection (only Ig M positive) was observed in 15% cases while rest 85% were secondary dengue infection (either Ig G or both Ig M and Ig G positive). Classical dengue fever (DF) was noted in 11% patients and 89% children presented with dengue hemorrhagic fever / dengue shock syndrome (DHF / DSS). Common clinical presentations were fever, headache, retro- orbital pain, arthralgia / bone pain, vomiting, abdominal pain and bleeding manifestations. Other presentations were tachycardia, bradycardia, hypotension, hepatomegaly, splenomegaly, pleural effusion, ascites, thrombocytopenia and high hematocrit values. The incidences of tachycardia, hypotension, hepatomegaly, high hematocrit and thrombocytopenia were significantly higher in DHF / DSS cases. The tourniquet test was positive in significantly higher percentage of DF cases. The tourniquet test and thrombocytopenia did not correlate well with other bleeding manifestations suggesting alternate pathogenesis for bleeding. In an epidemic setting, if a child presents with fever, vomiting, musculoskeletal pain and bleeding along with hepatomegaly, low platelet count and high hematocrit, a strong possibility of DHF/ DSS should be kept.

  8. Utility of the tourniquet test and the white blood cell count to differentiate dengue among acute febrile illnesses in the emergency room.

    PubMed

    Gregory, Christopher J; Lorenzi, Olga D; Colón, Lisandra; García, Arleene Sepúlveda; Santiago, Luis M; Rivera, Ramón Cruz; Bermúdez, Liv Jossette Cuyar; Báez, Fernando Ortiz; Aponte, Delanor Vázquez; Tomashek, Kay M; Gutierrez, Jorge; Alvarado, Luisa

    2011-12-01

    Dengue often presents with non-specific clinical signs, and given the current paucity of accurate, rapid diagnostic laboratory tests, identifying easily obtainable bedside markers of dengue remains a priority. Previous studies in febrile Asian children have suggested that the combination of a positive tourniquet test (TT) and leucopenia can distinguish dengue from other febrile illnesses, but little data exists on the usefulness of these tests in adults or in the Americas. We evaluated the diagnostic accuracy of the TT and leucopenia (white blood cell count <5000/mm(3)) in identifying dengue as part of an acute febrile illness (AFI) surveillance study conducted in the Emergency Department of Saint Luke's Hospital in Ponce, Puerto Rico. From September to December 2009, 284 patients presenting to the ED with fever for 2-7 days and no identified source were enrolled. Participants were tested for influenza, dengue, leptospirosis and enteroviruses. Thirty-three (12%) patients were confirmed as having dengue; 2 had dengue co-infection with influenza and leptospirosis, respectively. An infectious etiology was determined for 141 others (136 influenza, 3 enterovirus, 2 urinary tract infections), and 110 patients had no infectious etiology identified. Fifty-two percent of laboratory-positive dengue cases had a positive TT versus 18% of patients without dengue (P<0.001), 87% of dengue cases compared to 28% of non-dengue cases had leucopenia (P<0.001). The presence of either a positive TT or leucopenia correctly identified 94% of dengue patients. The specificity and positive predictive values of these tests was significantly higher in the subset of patients without pandemic influenza A H1N1, suggesting improved discriminatory performance of these tests in the absence of concurrent dengue and influenza outbreaks. However, even during simultaneous AFI outbreaks, the absence of leucopenia combined with a negative tourniquet test may be useful to rule out dengue.

  9. Utility of the Tourniquet Test and the White Blood Cell Count to Differentiate Dengue among Acute Febrile Illnesses in the Emergency Room

    PubMed Central

    Gregory, Christopher J.; Lorenzi, Olga D.; Colón, Lisandra; Sepúlveda García, Arleene; Santiago, Luis M.; Cruz Rivera, Ramón; Cuyar Bermúdez, Liv Jossette; Ortiz Báez, Fernando; Vázquez Aponte, Delanor; Tomashek, Kay M.; Gutierrez, Jorge; Alvarado, Luisa

    2011-01-01

    Dengue often presents with non-specific clinical signs, and given the current paucity of accurate, rapid diagnostic laboratory tests, identifying easily obtainable bedside markers of dengue remains a priority. Previous studies in febrile Asian children have suggested that the combination of a positive tourniquet test (TT) and leucopenia can distinguish dengue from other febrile illnesses, but little data exists on the usefulness of these tests in adults or in the Americas. We evaluated the diagnostic accuracy of the TT and leucopenia (white blood cell count <5000/mm3) in identifying dengue as part of an acute febrile illness (AFI) surveillance study conducted in the Emergency Department of Saint Luke's Hospital in Ponce, Puerto Rico. From September to December 2009, 284 patients presenting to the ED with fever for 2–7 days and no identified source were enrolled. Participants were tested for influenza, dengue, leptospirosis and enteroviruses. Thirty-three (12%) patients were confirmed as having dengue; 2 had dengue co-infection with influenza and leptospirosis, respectively. An infectious etiology was determined for 141 others (136 influenza, 3 enterovirus, 2 urinary tract infections), and 110 patients had no infectious etiology identified. Fifty-two percent of laboratory-positive dengue cases had a positive TT versus 18% of patients without dengue (P<0.001), 87% of dengue cases compared to 28% of non-dengue cases had leucopenia (P<0.001). The presence of either a positive TT or leucopenia correctly identified 94% of dengue patients. The specificity and positive predictive values of these tests was significantly higher in the subset of patients without pandemic influenza A H1N1, suggesting improved discriminatory performance of these tests in the absence of concurrent dengue and influenza outbreaks. However, even during simultaneous AFI outbreaks, the absence of leucopenia combined with a negative tourniquet test may be useful to rule out dengue. PMID:22163057

  10. 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

  11. Dengue virus infection: current concepts in immune mechanisms and lessons from murine models.

    PubMed

    Guabiraba, Rodrigo; Ryffel, Bernhard

    2014-02-01

    Dengue viruses (DENV), a group of four serologically distinct but related flaviviruses, are responsible for one of the most important emerging viral diseases. This mosquito-borne disease has a great impact in tropical and subtropical areas of the world in terms of illness, mortality and economic costs, mainly due to the lack of approved vaccine or antiviral drugs. Infections with one of the four serotypes of DENV (DENV-1-4) result in symptoms ranging from an acute, self-limiting febrile illness, dengue fever, to severe dengue haemorrhagic fever or dengue shock syndrome. We reviewed the existing mouse models of infection, including the DENV-2-adapted strain P23085. The role of CC chemokines, interleukin-17 (IL-17), IL-22 and invariant natural killer T cells in mediating the exacerbation of disease in immune-competent mice is highlighted. Investigations in both immune-deficient and immune-competent mouse models of DENV infection may help to identify key host–pathogen factors and devise novel therapies to restrain the systemic and local inflammatory responses associated with severe DENV infection.

  12. Primary dengue infection: what are the clinical distinctions from secondary infection?

    PubMed

    Pancharoen, C; Mekmullica, J; Thisyakorn, U

    2001-09-01

    To determine the magnitude of the problem posed by primary dengue infection in children and the distinctive clinical clues that may differ from those with secondary infection, 996 children serologically diagnosed with dengue infection and admitted to the Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand between 1988 and 1995 were retrospectively reviewed. One hundred and thirty-nine cases (14.0%) were serologically proved to be primary dengue infection. Of these, 72 were males and 67 were females, with a mean age of 4.8 years. Common manifestations by order of frequency included fever (97.8%), hepatomegaly (71.9%), vomiting (59.0%), decreased appetite (55.4%), coryza (52.5%), drowsiness (39.6%), diarrhea (34.5%), rash (33.8%), abdominal pain (23.0%) and seizure (15.8%). The mean duration of fever before admission was 4.6 days. Common sites of bleeding were skin (41.7%), mucous membrane (14.4%) and the gastrointestinal tract (12.2%). Clinical diagnosis was categorized into dengue fever (22.3%), dengue hemorrhagic fever (60.4%) and dengue shock syndrome (17.3%). Three patients (2.2%) died. Compared with the children with secondary dengue infection (n=139), children with primary dengue infections tended to be younger, presented more commonly with coryza, diarrhea, rash and seizure; and less commonly with vomiting, headache and abdominal pain (p < 0.05). The maximal hematocrit level, the mean difference between maximal and minimal hematocrit values and the maximal percentage of neutrophils were significantly lower in the study group, whereas the maximal percentage of lymphocytes was significantly higher. Dengue fever was more common and dengue shock syndrome was less common in the study group (p < 0.05). This study has emphasized that primary dengue infection is not uncommon and is less severe than secondary infection. Clinical presentations and laboratory findings are somewhat different between the two conditions.

  13. VEGF and its receptors in dengue virus infection.

    PubMed

    Kalita, J; Chauhan, P S; Mani, V E; Bhoi, S K; Misra, U K

    2015-09-01

    Vascular permeability determines the severity of dengue virus infection. Vascular endothelial growth factor (VEGF) and its (receptor 1) R1 and (receptor 2) R2 receptors may provide insight about the neurological complications of dengue. We report VEGF and its R1 and R2 receptors level in dengue patients and correlate these with neurological complications. Consecutive patients with dengue were subjected to clinical and neurological evaluations. Their blood counts, serum chemistry, including liver and kidney function tests, serum creatine kinase (CK), and albumin were measured. VEGF, VEGFR1 and VEGFR2 were measured by ELISA in the patients and 16 matched controls. Twenty four patients with dengue were included whose ages ranged between 15 and 67 years, and nine of whom were females. Serum VEGF level was insignificantly lower in dengue patients whereas VEGFR1 was significantly higher (P = 0.01) and VEGFR2 was significantly lower (P = 0.005) compared to controls. VEGFR2 correlated with systolic blood pressure, coagulopathy, and serum CK levels. None of the other clinical and biochemical parameters correlated with VEGF and VEGFR1 levels. VEGFR1 and R2 normalized at 1 month. VEGFR2 correlates with the clinical severity of dengue and muscle dysfunction.

  14. Occurrence and Correlates of Symptom Persistence Following Acute Dengue Fever in Peru

    PubMed Central

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

    2014-01-01

    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. PMID:24470564

  15. 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.

  16. HLA-A and -B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais.

    PubMed

    Stephens, H A F; Klaythong, R; Sirikong, M; Vaughn, D W; Green, S; Kalayanarooj, S; Endy, T P; Libraty, D H; Nisalak, A; Innis, B L; Rothman, A L; Ennis, F A; Chandanayingyong, D

    2002-10-01

    Little is known of the role of classical HLA-A and -B class I alleles in determining resistance, susceptibility, or the severity of acute viral infections. Appropriate paradigms for immunogenetic studies of acute viral infections are dengue fever (DF) and dengue hemorrhagic fever (DHF). Both primary and secondary infections with dengue virus (DEN) serotypes 1, 2, 3 or 4, can result in either clinically less severe DF or the more severe DHF. In secondary exposures, a memory response is induced in immunologically primed individuals, which can both clear the infecting dengue virus and contribute to its pathology. In a case-control study of 263 ethnic Thai patients infected with either DEN-1, -2, -3 or -4, we detected HLA class I associations with secondary infections, but not in immunologically naive patients with primary infections. HLA-A*0203 was associated with the less severe DF, regardless of the secondary infecting virus serotype. By contrast, HLA-A*0207 was associated with susceptibility to the more severe DHF in patients with secondary DEN-1 and DEN-2 infections only. Conversely, HLA-B*51 was associated with the development of DHF in patients with secondary infections, and HLA-B*52 was associated with DF in patients with secondary DEN-1 and DEN-2 infections. Moreover, HLA-B44, B62, B76 and B77 also appeared to be protective against developing clinical disease after secondary dengue virus infection. These results confirm that classical HLA class I alleles are associated with the clinical outcome of exposure to dengue virus, in previously exposed and immunologically primed individuals.

  17. Ultrastructural studies on dengue virus infection of human lymphoblasts.

    PubMed Central

    Sriurairatna, S; Bhamarapravati, N; Diwan, A R; Halstead, S B

    1978-01-01

    Ultrastructural studies of dengue-2 virus-infected lymphoblastoid Raji cells showed that the virus induced an increase in the size of the rough endoplasmic reticula (RER) and that the replication of the virus was confined to the cisternae of these RER. The proliferating RER formed cytoplasmic inclusions that could be seen by light microscopy. This observation could be used as evidence of a cytopathogenic effect of dengue virus on infected Rajii cells in routine cultures. Accumulation of virions in the infected cells was minimal in comparison with other cell systems, however. Sporadic clusters of mature virions were often seen on the plasma membrane. These extracellular virions were distributed adjacent to the virus-bearing RER and were presumably released virions. Vertical transmission of the virus was evident in mitotic lymphoblasts. The replication pattern of dengue virus in lymphoblastoid cells suggests that efforts should be made to determine whether blast-transformed lymphocytes, numerous in secondary dengue infections, support dengue virus replication in vivo. Images PMID:669791

  18. Serum levels of cytokines in two ethnic groups with dengue virus infection.

    PubMed

    Restrepo, Berta N; Ramirez, Ruth E; Arboleda, Margarita; Alvarez, Gonzalo; Ospina, Marta; Diaz, Francisco J

    2008-11-01

    This study compared the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interferon gamma (IFN-gamma) in 78 Colombian patients, from two ethnic groups, with dengue virus infection. TNF-alpha levels were significantly higher in Afro-Colombians than in Mestizos and IL-6 levels were significantly higher in Mestizos than in Afro-Colombians, during the acute phase. IFN-gamma levels were similar in both ethnic groups. Significantly higher TNF-alpha levels were found in Afro-Colombians than in Mestizos in both dengue fever (DF) and dengue hemorrhagic fever (DHF). The IL-6 levels were higher in Mestizos than in Afro-Colombians among patients with DF, but levels of this cytokine were higher in Afro-Colombians than in Mestizos among patients with DHF. Levels of IFN-gamma were higher in patients with DHF than DF. Higher levels of these cytokines were observed in secondary infection. These results suggest that ethnicity may contribute to differences in immune responses to dengue infections.

  19. Early dengue virus interactions: the role of dendritic cells during infection.

    PubMed

    Santos Souza, Higo Fernando; da Silva Almeida, Bianca; Boscardin, Silvia Beatriz

    2016-09-01

    Dengue is an acute infectious disease caused by dengue virus (DENV) that affects approximately 400 million people annually, being the most prevalent human arthropod-borne disease. DENV infection causes a wide variety of clinical manifestations that range from asymptomatic to dengue fever, and in some cases may evolve to the more severe dengue hemorrhagic fever and dengue shock syndrome. The exact reasons why some patients do not have symptoms while others develop the severe forms of disease are still elusive, but gathered evidence showed correlation between a secondary infection with a heterologous DENV serotype and the occurrence of severe symptoms. Despite several advances, the mechanisms of DENV infection are still not completely elucidated, and efforts have been made to understand the development of immunity and/or pathology to DENV. When a mosquito transmits DENV, the virus is initially deposited in the skin, where mononuclear phagocytic cells, such as dendritic cells (DCs), become infected. DCs play a critical role in the induction of immune responses, as they are able to rapidly detect pathogen-associated molecular patterns, endocytose and process antigens, and efficiently activate naïve-T and B cells. Recent findings have shown that DCs serve as DENV targets, but they are also important mediators of immunity against the virus. In this review, we will briefly discuss DENV infection pathogenesis, and introduce DCs as central players in the induction of anti-DENV immune responses. Then, we will review in more detail how DENV interacts with and is sensed by DCs, with particular emphasis in two classes of receptors implicated in viral entry. PMID:27381061

  20. Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

    PubMed Central

    Punyadee, Nuntaya; Mairiang, Dumrong; Thiemmeca, Somchai; Komoltri, Chulaluk; Pan-ngum, Wirichada; Chomanee, Nusara; Charngkaew, Komgrid; Tangthawornchaikul, Nattaya; Limpitikul, Wannee; Vasanawathana, Sirijitt; Malasit, Prida

    2014-01-01

    ABSTRACT Shedding of microparticles (MPs) is a consequence of apoptotic cell death and cellular activation. Low levels of circulating MPs in blood help maintain homeostasis, whereas increased MP generation is linked to many pathological conditions. Herein, we investigated the role of MPs in dengue virus (DENV) infection. Infection of various susceptible cells by DENV led to apoptotic death and MP release. These MPs harbored a viral envelope protein and a nonstructural protein 1 (NS1) on their surfaces. Ex vivo analysis of clinical specimens from patients with infections of different degrees of severity at multiple time points revealed that MPs generated from erythrocytes and platelets are two major MP populations in the circulation of DENV-infected patients. Elevated levels of red blood cell-derived MPs (RMPs) directly correlated with DENV disease severity, whereas a significant decrease in platelet-derived MPs was associated with a bleeding tendency. Removal by mononuclear cells of complement-opsonized NS1–anti-NS1 immune complexes bound to erythrocytes via complement receptor type 1 triggered MP shedding in vitro, a process that could explain the increased levels of RMPs in severe dengue. These findings point to the multiple roles of MPs in dengue pathogenesis. They offer a potential novel biomarker candidate capable of differentiating dengue fever from the more serious dengue hemorrhagic fever. IMPORTANCE Dengue is the most important mosquito-transmitted viral disease in the world. No vaccines or specific treatments are available. Rapid diagnosis and immediate treatment are the keys to achieve a positive outcome. Dengue virus (DENV) infection, like some other medical conditions, changes the level and composition of microparticles (MPs), tiny bag-like structures which are normally present at low levels in the blood of healthy individuals. This study investigated how MPs in culture and patients' blood are changed in response to DENV infection. Infection of cells

  1. 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

  2. Phage-displayed antibody fragments recognizing dengue 3 and dengue 4 viruses as tools for viral serotyping in sera from infected individuals.

    PubMed

    Cabezas, Sheila; Rojas, Gertrudis; Pavon, Alequis; Bernardo, Lidice; Castellanos, Yinet; Alvarez, Mayling; Pupo, Maritza; Guillen, Gerardo; Guzman, Maria G

    2009-01-01

    The current study shows the usefulness of dengue-3- and dengue-4-specific phage-displayed antibody fragments as tools for viral detection and serotyping in sera from infected individuals. C6/36 HT cells were inoculated with acute-phase sera from patients, and supernatants were collected daily and analyzed by ELISA using phage-displayed antibody fragments as serotype-specific detector reagents. Serotyping of most samples was possible as early as two to three days postinoculation. Results were comparable with those obtained by indirect immunofluorescence assay but were obtained in a shorter period of time (<1 week). Phage-displayed antibody fragments were better tools for diagnosis and serotyping than their soluble counterparts. Our approach combines the advantages of viral isolation and ELISA techniques. These results could be the basis for the development of a high-throughput method for identifying dengue virus serotypes, which is crucial for the management and control of the disease.

  3. Concurrent dengue and malaria in Cayenne Hospital, French Guiana.

    PubMed

    Carme, Bernard; Matheus, Severine; Donutil, Gerd; Raulin, Olivia; Nacher, Mathieu; Morvan, Jacques

    2009-04-01

    Dengue-malaria co-infection reports are scarce. Of 1,723 consecutive febrile patients in Cayenne Hospital, 238 had dengue (174 early dengue fever cases) and 393 had malaria (371 acute malaria); 17 had both. Diagnosis of 1 of these 2 infections should not rule out testing for the other infection.

  4. In vivo infection by a neuroinvasive neurovirulent dengue virus.

    PubMed

    Velandia-Romero, Myriam Lucia; Acosta-Losada, Orlando; Castellanos, Jaime E

    2012-10-01

    Although neurological manifestations associated with dengue infections have been reported in endemic countries, the viral or host characteristics determining the infection or alteration of nervous function have not been described. In order to investigate neurobiological conditions related to central nervous system dengue virus (DENV) infection, we established a mouse model of neuroinfection. A DENV-4 isolate was first adapted to neuroblastoma cells, later inoculated in suckling mice brain, and finally, this D4MB-6 viral variant was inoculated intraperitoneally in Balb/c mice at different postnatal days (pnd). Virus-induced fatal encephalitis in 2 and 7 pnd mice but infected at 14 and 21 pnd mice survived. The younger mice presented encephalitis at the sixth day postinfection with limb paralysis and postural instability concomitant with efficient viral replication in brain. In this mice model, we found activated microglial cells positive to viral antigen. Neurons, oligodendrocytes, and endothelial cells were also infected by the D4MB-6 virus in neonatal mice, which showed generalized and local plasma leakage with blood-brain barrier (BBB) severe damage. These results suggest that there was a viral fitness change which led to neuroinfection only in immune or neurological immature mice. Infection of neurons, endothelial, and microglial cells may be related to detrimental function or architecture found in susceptible mice. This experimental neuroinfection model could help to have a better understanding of neurological manifestations occurring during severe cases of dengue infection.

  5. Characteristics of mild dengue virus infection in Thai children.

    PubMed

    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

    2013-12-01

    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.

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

    PubMed

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

    2016-01-01

    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

  7. 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

  8. Acute kidney injury in dengue fever using Acute Kidney Injury Network criteria: incidence and risk factors.

    PubMed

    Mehra, Nikita; Patel, Amish; Abraham, Georgi; Reddy, Yogesh N V; Reddy, Yuvaram N V

    2012-07-01

    The aim of this study was to assess incidence and risk factors for acute kidney injury (AKI) in patients with dengue fever (DF). A total of 223 patients (males, 130; females, 93; mean age, 26.2 ± 18.2 years) from a tertiary care centre in southern India were retrospectively analysed. Acute renal failure (ARF) developed in 24 (10.8%) patients. Based on the Acute Kidney Injury Network (AKIN) criteria, the results revealed that: 12 (5.4%) had mild AKI; seven (3.1%) had moderate AKI; and five (2.2%) had severe AKI. A further 54 (24%) were diagnosed with dengue haemorrhagic fever (DHF); 11 (5%) were co-infected with leptospirosis; thrombocytopenia was present in 157 (70%); and 64 (29%) were hypotensive. Patients were divided into either group A (with AKI) or group B (without AKI), and group A was divided into mild (A1), moderate (A2) and severe (A3) subgroups. We recorded: a higher total white count (A = 9824; B = 6706; P = 0.01); serum glutamic pyruvic transaminase (SGPT; A = 450; B = 144; P = 0.001); alkaline phosphatase (ALP) levels (A = 207; B = 42; P = 0.001); lower albumin (A = 2.65; B = 3.09; P < 0.001); and serum bicarbonate (A = 20.57; B = 23.21; P = 0.009). Hypotension (P = 0.01), coexisting viral hepatitis (P < 0.001), sepsis (P < 0.001), multiple organ dysfunction syndrome (MODS; P < 0.001) and the need for inotropes (P < 0.001) were associated with DF. Total white count (P = 0.038), glomerular filtration rate (GFR) on discharge (P = 0.034), specific gravity of urine (P = 0.006), ALP (P = 0.013), SGPT (P = 0.042), MODS (P = 0.05) and use of platelet fresh frozen plasma (FFP; P = 0.007) were significantly different between mild, moderate and severe AKI subgroups. Twenty-two (9%) died. AKI is associated with an increased mortality in DF (P = 0.005).

  9. 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.

  10. Dengue virus-infected Aedes aegypti in the home environment.

    PubMed

    Garcia-Rejon, Julian; Loroño-Pino, Maria Alba; Farfan-Ale, Jose Arturo; Flores-Flores, Luis; Del Pilar Rosado-Paredes, Elsy; Rivero-Cardenas, Nubia; Najera-Vazquez, Rosario; Gomez-Carro, Salvador; Lira-Zumbardo, Victor; Gonzalez-Martinez, Pedro; Lozano-Fuentes, Saul; Elizondo-Quiroga, Darwin; Beaty, Barry J; Eisen, Lars

    2008-12-01

    We determined abundance of Aedes aegypti mosquitoes and presence of dengue virus (DENV) in females collected from premises of laboratory-confirmed dengue patients over a 12-month period (March 2007 to February 2008) in Merida, Mexico. Backpack aspiration from 880 premises produced 1,836 females and 1,292 males indoors (predominantly from bedrooms) and 102 females and 108 males from patios/backyards. The mean weekly indoor catch rate per home peaked at 7.8 females in late August. Outdoor abundances of larvae or pupae were not predictive of female abundance inside the home. DENV-infected Ae. aegypti females were recovered from 34 premises. Collection of DENV-infected females from homes of dengue patients up to 27 days after the onset of symptoms (median, 14 days) shows the usefulness of indoor insecticide application in homes of suspected dengue patients to prevent their homes from becoming sources for dispersal of DENV by persons visiting and being bitten by infected mosquitoes. PMID:19052309

  11. Current and nano-diagnostic tools for dengue infection.

    PubMed

    Peh, Alister En Kai; Leo, Yee-Sin; Toh, Chee Seng

    2011-01-01

    Dengue is one of the infectious diseases that is widespread over global regions with yearly occurrence of epidemics and could be deadly in some cases. Thus the developments of rapid and specific diagnostic tools which can achieve early detection of dengue infection for disease control during epidemic situations and before complications occur are deemed highly desirable. This paper describes the current and advanced methods for diagnosis of dengue infection and discusses the advantages and disadvantages of these methods in terms of their analytical performances and clinical applicabilities. The current methods discussed herein include enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. In addition, recent instrumental methods such as quartz crystal microbalance, surface plasmon resonance, photonic crystal and electrochemical impedance spectroscopy have shown promising results. Interesting developments in detection of dengue infection using nanosized materials including liposomes, nanowires and nanopores, coupled to conventional fluorescence, potentiometry and voltammetry methods are also described and could possibly point the way forward for the development of inexpensive diagnostic tools for use at point-of-care and in events of epidemic scale.

  12. Advances and new insights in the neuropathogenesis of dengue infection.

    PubMed

    Puccioni-Sohler, Marzia; Rosadas, Carolina

    2015-08-01

    Dengue virus (DENV) infects approximately 390 million persons every year in more than 100 countries. Reports of neurological complications are more frequently. The objective of this narrative review is to bring up the advances in the dengue neuropathogenesis. DENV can access the nervous system through blood-brain barrier disturbance mediated by cytokine. The blood-cerebrospinal fluid (CSF) barrier seems to be also involved, considering the presence of the virus in the CSF of patients with neurological manifestations. As for neurotropism, several studies showed the presence of RNA and viral antigens in brain tissue and CSF in humans. In murine model, different virus mutations were associated to neurovirulence. Despite the advances in the dengue neuropathogenesis, it is still necessary to determine a more appropriate animal model and increase the number of cases of autopsy. The detection of neurovirulence markers may contribute to establish a prognosis, the disease control and vaccine development. PMID:26222363

  13. Association between nutritional status and severity of dengue infection in children in El Salvador.

    PubMed

    Marón, Gabriela M; Clará, A Wilfrido; Diddle, John Wesley; Pleités, Ernesto B; Miller, Laura; Macdonald, Gene; Adderson, Elisabeth E

    2010-02-01

    Clinical observations and some studies suggest that dengue virus infection is more severe among children with better nutritional status. We examined the nutritional status of children in El Salvador and its relationship between this and the severity of dengue infection. Z-scores for weight-for-age, height-for-age, and body mass index (BMI)-for-age of children with dengue fever (66), dengue hemorrhagic fever (62), and healthy controls (74) were compared. There were no differences in weight-for-age or BMI-for-age Z-scores between the three groups. Children with dengue fever had a greater height-for-age than healthy controls but no significant differences in rates of stunting. There was no difference in height between children with dengue fever and dengue hemorrhagic fever. Excess nutrition does not appear to be a risk factor for severe forms of dengue infection in El Salvador, nor does malnutrition appear to be predictive of good outcomes.

  14. Dengue and dengue haemorrhagic fever.

    PubMed

    Rigau-Pérez, J G; Clark, G G; Gubler, D J; Reiter, P; Sanders, E J; Vorndam, A V

    1998-09-19

    The incidence and geographical distribution of dengue have greatly increased in recent years. Dengue is an acute mosquito-transmitted viral disease characterised by fever, headache, muscle and joint pains, rash, nausea, and vomiting. Some infections result in dengue haemorrhagic fever (DHF), a syndrome that in its most severe form can threaten the patient's life, primarily through increased vascular permeability and shock. The case fatality rate in patients with dengue shock syndrome can be as high as 44%. For decades, two distinct hypotheses to explain the mechanism of DHF have been debated-secondary infection or viral virulence. However, a combination of both now seems to be the plausible explanation. The geographical expansion of DHF presents the need for well-documented clinical, epidemiological, and virological descriptions of the syndrome in the Americas. Biological and social research are essential to develop effective mosquito control, medications to reduce capillary leakage, and a safe tetravalent vaccine.

  15. Acute upper airway infections.

    PubMed

    West, J V

    2002-01-01

    Upper respiratory tract infections are common and important. Although rarely fatal, they are a source of significant morbidity and carry a considerable economic burden. Numerous therapies for the common cold have no effect on symptoms or outcome. Complications such as cough are not improved by over-the-counter preparations, while labelling cough alone as a symptom of asthma may result in unnecessary use of inhaled steroid treatment. Clinical presentation of sore throat does not accurately predict whether the infection is viral or bacterial, while throat culture and rapid antigen tests do not significantly change prescribing practice. Antibiotics have only a limited place in the management of recurrent sore throat due to group A beta-haemolytic streptococcal infection. Routine use of antibiotics in upper respiratory infection enhances parent belief in their effectiveness and increases the likelihood of future consultation in primary care for minor self-limiting illness. Respiratory viruses play a major role in the aetiology of acute otitis media (AOM); prevention includes the use of influenza or RSV vaccination, in addition to reducing other risk factors such as early exposure to respiratory viruses in day-care settings and to environmental tobacco smoke. The use of ventilation tubes (grommets) in secretory otitis media (SOM) remains controversial with conflicting data on developmental outcome and quality of life in young children. New conjugate pneumococcal vaccines appear safe in young children and prevent 6-7% of clinically diagnosed AOM.

  16. 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

  17. 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. PMID:27223651

  18. Incidence, Characteristics and Risk Factors of Acute Kidney Injury among Dengue Patients: A Retrospective Analysis

    PubMed Central

    Mallhi, Tauqeer Hussain; Khan, Amer Hayat; Adnan, Azreen Syazril; Sarriff, Azmi; Khan, Yusra Habib; Jummaat, Fauziah

    2015-01-01

    Background Dengue induced acute kidney injury (AKI) imposes heavy burden of illness in terms of morbidity and mortality. A retrospective study was conducted to investigate incidence, characteristics, risk factors and clinical outcomes of AKI among dengue patients. Methodology A total 667 dengue patients (2008–2013) were retrospectively evaluated and were stratified into AKI and non-AKI groups by using AKIN criteria. Two groups were compared by using appropriate statistical methods. Results There were 95 patients (14.2%) who had AKI, with AKIN-I, AKIN-II and AKIN-III in 76.8%, 16.8% and 6.4% patients, respectively. Significant differences (P<0.05) in demographics and clinico-laboratory characteristics were observed between patients with and without AKI. Presence of dengue hemorrhagic fever [OR (95% CI): 8.0 (3.64–17.59), P<0.001], rhabdomyolysis [OR (95% CI): 7.9 (3.04–20.49)], multiple organ dysfunction [OR (95% CI): 34.6 (14.14–84.73), P<0.001], diabetes mellitus [OR (95% CI): 4.7 (1.12–19.86), P = 0.034], late hospitalization [OR (95% CI): 2.1 (1.12–19.86), P = 0.033] and use of nephrotoxic drugs [OR (95% CI): 2.9 (1.12–19.86), P = 0.006] were associated with AKI. Longer hospital stay (>3 days) was also observed among AKI patients (OR = 1.3, P = 0.044). Additionally, 48.4% AKI patients had renal insufficiencies at discharge that were signicantly associated with severe dengue, secondary infection and diabetes mellitus. Overall mortality was 1.2% and all fatal cases had AKI. Conclusions The incidence of AKI is high at 14.2% among dengue patients, and those with AKI portended significant morbidity, mortality, longer hospital stay and poor renal outcomes. Our findings suggest that AKI in dengue is likely to increase healthcare burden that underscores the need of clinicians’ alertness to this highly morbid and potentially fatal complication for optimal prevention and management. PMID:26421839

  19. 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

    Phanthanawiboon, Supranee; Limkittikul, Kriengsak; Sakai, Yusuke; Takakura, Nobuyuki; Saijo, Masayuki; Kurosu, Takeshi

    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

  20. 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

  1. 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

    Phanthanawiboon, Supranee; Limkittikul, Kriengsak; Sakai, Yusuke; Takakura, Nobuyuki; Saijo, Masayuki; Kurosu, Takeshi

    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.

  2. ELEVATED LEVELS OF SOLUBLE ST2 PROTEIN IN DENGUE VIRUS INFECTED PATIENTS

    PubMed Central

    Becerra, Aniuska; Warke, Rajas V.; de Bosch, Norma; Rothman, Alan L.; Bosch, Irene

    2008-01-01

    Levels of the soluble form of the interleukin-1 receptor like 1 protein (IL-1RL-1 / ST2) are elevated in the serum of patients with diseases characterized by an inflammatory response. The objective of this study was to determine the concentration of soluble ST2 (sST2) in dengue infected patients during the course of the disease. Twenty four patients with confirmed dengue infection, classified as dengue fever, and eleven patients with other febrile illness (OFI) were evaluated. Levels of sST2 in serum and laboratory variables usually altered during dengue infections were measured. Dengue infected patients had higher serum sST2 levels than OFI at the end of the febrile stage and at defervescence (p=0.0088 and p=0.0004 respectively). Patients with secondary dengue infections had higher serum sST2 levels compared with patients with primary dengue infections (p=0.047 at last day of fever and p=0.030 at defervescence). Furthermore, in dengue infected patients, we found a significant negative correlation of sST2 with platelet and WBC counts, and positive correlation with thrombin time and transaminases activity. We suggest that sST2 could be a potential marker of dengue infection, could be associated with severity or could play a role in the immune response in secondary dengue virus infection. PMID:18226917

  3. Association of MICA and MICB alleles with symptomatic dengue infection.

    PubMed

    García, Gissel; del Puerto, Florencia; Pérez, Ana B; Sierra, Beatriz; Aguirre, Eglys; Kikuchi, Mihoko; Sánchez, Lizet; Hirayama, Kenji; Guzmán, María G

    2011-10-01

    Dengue viruses (DV) are one of the most important arthropod-borne viral diseases in the developing world. DV can cause syndromes that are either self-limiting or severe. Allelic variants of human leukocyte antigen (HLA) genes have been demonstrated to be associated with disease susceptibility. Here we report the association of nonclassical HLA class I MICA-MICB genes with disease outcome during DV infection. A sequencing-based typing method and genotyping of MICA and MICB in a well-characterized group of Cuban individuals with dengue hemorrhagic fever (DHF), dengue fever (DF), or asymptomatic dengue infection (ADI) was performed. Statistical analysis revealed a tendency for MICA*008 and MICB*008 to associate with susceptibility to illness when symptomatic versus asymptomatic cases (odds ratio [OR] = 2.1, p(v) = 0.03, and OR = 10.4, p = 0.0096, respectively) were compared. Surprisingly, a stronger association of both allelic forms was observed for the DF patients compared with the ADI group (MICA*008, OR = 5.2, p = 0.0001; and MICB*008, OR = 13.2, p = 0.0025) rather than the severe cases. Major histocompatibility class I-related gene-related natural killer cells and/or γδ and αβ T-cell activation might regulate the development of symptomatic DF and DHF.

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

    PubMed

    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

    2016-07-12

    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

  5. 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

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

    PubMed

    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

    2016-07-12

    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.

  7. Serum proteome changes in dengue virus-infected patients from a dengue-endemic area of India: towards new molecular targets?

    PubMed

    Ray, Sandipan; Srivastava, Rajneesh; Tripathi, Karnika; Vaibhav, Vineet; Patankar, Swati; Srivastava, Sanjeeva

    2012-10-01

    The global burden of dengue continues to worsen, specifically in tropical and subtropical countries, and has evolved as a major public health problem. We investigated the changes in serum proteome in dengue fever (DF) patients from a dengue-endemic area of India to obtain mechanistic insights about the disease pathogenesis, the host immune response, and identification of potential serum protein biomarkers of this infectious disease. In this study, serum samples from DF patients, healthy subjects, and patients with falciparum malaria (an infectious disease control) were investigated by 2D-DIGE in combination with MALDI-TOF/TOF MS. The findings were validated with Western blotting. Functional clustering of the identified proteins was performed using PANTHER and DAVID tools. Compared to the healthy controls, we found significant changes in the expression levels of 48 protein spots corresponding to 18 unique proteins (7 downregulated and 11 upregulated) in DF patients (p<0.05). Among these differentially-expressed proteins, 11 candidates exhibited different trends in dengue fever compared to falciparum malaria. Importantly, our results suggest that dengue virus infection leads to alterations in expression levels of multiple serum proteins involved in diverse and vital physiological pathways, including acute phase response signaling, complement cascades, hemostasis, and blood coagulation. For the first time we report here that the serum levels of hemopexin, haptoglobin, serum amyloid P, and kininogen precursor, are altered in DF. This study informs the pathogenesis and host immune response to dengue virus infection, as well as the current search for new diagnostic and molecular drug targets.

  8. Meningitis determined by oligosymptomatic dengue virus type 3 infection: report of a case.

    PubMed

    Soares, C N; Cabral-Castro, M J; Peralta, J M; Freitas, M R G; Puccioni-Sohler, M

    2010-02-01

    Dengue infection is a mosquito-borne disease caused by a flavivirus, and is recognized in over 100 countries with 2.5 billion people living in areas of risk. Neurological manifestations such as encephalitis, myelitis, Guillain-Barré syndrome, cranial nerve palsies, neuromyelitis optica, and encephalomyelitis have been recognized as clinical consequences of dengue infection. Meningitis is a rare complication. We report the case of a 24-year-old woman who presented with fever, headache, and nuchal rigidity without the typical symptoms of dengue infection. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with a normal glucose value and negative bacterial and fungal cultures. The etiology of meningitis was confirmed by positive dengue PCR in the serum. This case report highlights dengue infection as a potential cause of meningitis in endemic areas. Also, meningitis can be the first manifestation of the infection. Dengue should be investigated even in the absence of a typical picture of the infection.

  9. Spontaneously resolving cerebellar syndrome as a sequelae of dengue viral infection: a case series from Sri Lanka.

    PubMed

    Weeratunga, Praveen N; Caldera, H P Manjula C; Gooneratne, I Kishara; Gamage, Ranjanie; Perera, W Sujith P; Ranasinghe, Gayan V; Niraj, Mahboob

    2014-06-01

    Sri Lanka is hyperendemic for dengue viral infection. Dengue has a wide spectrum of neurological manifestations including previously reported Sri Lankan cases with a 6th nerve palsy and a cerebellar syndrome from a co-infection with dengue and Epstein-Barr virus. This series describes a spontaneously resolving cerebellar syndrome following a dengue viral infection. Dengue is potentially an important cause of cerebellar syndromes in countries hyperendemic for the disease; patients need further studies to identify the responsible serotypes.

  10. Fatal and mild primary dengue virus infections imported to Norway from Africa and south-east Asia, 2008-2010.

    PubMed

    Vainio, K; Noraas, S; Holmberg, M; Fremstad, H; Wahlstrøm, M; Anestad, G; Dudman, S

    2010-09-23

    Between 2008 and 2010, eight cases of viraemic dengue fever in travellers were diagnosed in Norway. They had returned from Eritrea, Thailand and Indonesia. All cases were primary dengue infections, seven non-complicated dengue fever and one dengue shock syndrome with a fatal outcome. Four patients were infected with dengue virus serotype 1, one with type 2 and three with type 3. Two cases from Thailand, the fatal case and the two imported from Eritrea were infected with type 1.

  11. Cardiac involvement in dengue virus infections during the 2004/2005 dengue fever season in Sri Lanka.

    PubMed

    Wichmann, Dominic; Kularatne, Senanayake; Ehrhardt, Stephan; Wijesinghe, Sriyal; Brattig, Norbert W; Abel, Walter; Burchard, Gerd D

    2009-07-01

    Sri Lanka experienced a dramatic increase in dengue cases (15,400) in the 2004 - 2005 season. We carried out a prospective study to investigate cardiac involvement in dengue virus infected patients during the 2004 - 2005 season in Peradeniya, Central Province, Sri Lanka. Cardiac involvement was defined as elevated levels of myoglobin, creatine kinase-muscle brain-type, N-terminal pro-brain natriuretic peptide, heart-type fatty acid-binding protein and troponin T. Twenty-five percent of dengue virus infected patients had one or more of the above tests with abnormal results.

  12. Gene expression profiling of dengue infected human primary cells identifies secreted mediators in vivo

    PubMed Central

    Becerra, Aniuska; Warke, Rajas V.; Martin, Katherine; Xhaja, Kris; de Bosch, Norma; Rothman, Alan L.; Bosch, Irene

    2009-01-01

    We used gene expression profiling of human primary cells infected in vitro with dengue virus (DENV) as a tool to identify secreted mediators induced in response to the acute infection. Affymetrix Genechip analysis of human primary monocytes, B cells and dendritic cells infected with DENV in vitro revealed a strong induction of monocyte chemotactic protein 2 (MCP-2/CCL8), interferon gamma-induced protein 10 (IP-10/CXCL10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10). The expression of these genes was confirmed in dendritic cells infected with DENV in vitro at mRNA and protein levels. A prospectively enrolled cohort of DENV-infected Venezuelan patients was used to measure the levels of these proteins in serum during three different periods of the disease. Results showed significant increase of MCP-2, IP-10 and TRAIL levels in DENV-infected patients during the febrile period, when compared to healthy donors and patients with other febrile illnesses. MCP-2 and IP-10 levels were still elevated during the post-febrile period while TRAIL levels dropped close to normal after defervescense. Patients with primary infections had higher TRAIL levels than patients with secondary infections during the febrile period of the disease. Increased levels of IP-10, TRAIL and MCP-2 in acute DENV infections suggest a role for these mediators in the immune response to the infection. PMID:19551822

  13. Dengue infections in the Philippines: clinical and virological findings in 517 hospitalized patients.

    PubMed

    Hayes, C G; Manaloto, C R; Gonzales, A; Ranoa, C P

    1988-07-01

    From May 1983 to January 1984, 517 patients with laboratory confirmed dengue were studied at a hospital in Manila. Secondary dengue infections were diagnosed in 78% of these cases. Peak admission (28%) occurred towards the end of the rainy season in November. Most patients (78%) were less than 15 years old but only 3 were infants. Although some type of hemorrhagic finding occurred in 460 cases (89%), only 110 were classified as dengue hemorrhagic fever and the remainder as dengue fever with hemorrhagic manifestations. The clinical course was usually mild. Gastrointestinal bleeding was present in 65 cases, but only 2 patients developed shock. No fatalities occurred. Dengue 2 was the predominant serotype with 53 isolates, followed by dengue 1 with 48 isolates, dengue 3 with 39 isolates, and dengue 4 with only 8 isolates. Dengue 2 was the only serotype with more isolates from sera with a homologous HI antibody titer greater than 1:20 (57%) than from sera with a homologous HI titer less than or equal to 1:20 (43%). In contrast, most of the dengue 1 isolates (63%) were from sera with a homologous HI antibody titer less than 1:10, and this serotype was strongly associated with primary infections. This study shows that dengue infections remain an important cause of pediatric hospitalization in the Philippines; however, the occurrence of life-threatening dengue hemorrhagic fever as has been described in several other large urban areas of Southeast Asia appears to be rare.

  14. Challenges in Dengue Fever in the Elderly: Atypical Presentation and Risk of Severe Dengue and Hospita-Acquired Infection

    PubMed Central

    Rowe, Emily K.; Leo, Yee-Sin; Wong, Joshua G. X.; Thein, Tun-Linn; Gan, Victor C.; Lee, Linda K.; Lye, David C.

    2014-01-01

    Background/methods To better understand dengue fever in the elderly, we compared clinical features, World Health Organization (WHO) dengue classification and outcomes between adult (<60) and elderly (≥60) dengue patients. We explored the impact of co-morbidity and hospital-acquired infection (HAI) on clinical outcomes in the elderly. All patients managed at the Communicable Disease Centre, Singapore, between 2005 and 2008 with positive dengue polymerase chain reaction (PCR) or who fulfilled WHO 1997 or 2009 probable dengue criteria with positive dengue IgM were included. Results Of the 6989 cases, 295 (4.4%) were elderly. PCR was positive in 29%. The elderly suffered more severe disease with more dengue haemorrhagic fever (DHF) (29.2% vs. 21.4%) and severe dengue (SD) (20.3% vs. 14.6%) (p<0.05). Classic dengue symptoms were more common in the adult group. The elderly were less likely to fulfill WHO 1997 (93.6% vs. 96.4%) (p = 0.014), but not WHO 2009 probable dengue (75.3% vs. 71.5%). Time to dengue diagnosis was similar. There was no significant difference in the frequency of warning signs between the two groups, but the elderly were more likely to have hepatomegaly (p = 0.006) and malaise/lethargy (p = 0.033) while the adults had significantly more mucosal bleeding (p<0.001). Intensive care admission occurred in 15 and death in three, with no age difference. Notably, the elderly stayed in hospital longer (median 5 vs. 4 days), and suffered more pneumonia (3.8% vs. 0.7%) and urinary infection (1.9% vs. 0.3%) (p = 0.003). Predictors of excess length of stay were age (adjusted odds ratio [aOR] 2.01, 95% confidence interval [CI] 1.37–2.88), critical illness (aOR 5.13, 95%CI 2.59–9.75), HAI (aOR 12.06, 95%CI 7.39–19.9), Charlson score (aOR 6.9, 95%CI 2.02–22.56) and severe dengue (DHF/dengue shock syndrome/SD) (aOR 2.24, 95%CI 1.83–2.74). Conclusion Elderly dengue patients present atypically and are at higher risk of DHF, SD and HAI. Aside

  15. 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

    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

    2016-07-01

    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

  16. Epidemiology of dengue infections in Kassala, Eastern Sudan.

    PubMed

    Abdallah, Tajeldin M; Ali, Abdel Aziem A; Karsany, Mubarak S; Adam, Ishag

    2012-03-01

    Eighty-one (71.7%) out of 113 patients had confirmed dengue infection (using ELISA IgM serology) at Kassala, Eastern Sudan during the period of August through November 2010. According to the WHO criteria, dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) were observed in 30.9, 58, and 11.1% of these patients, respectively. The mean age of these 81 patients was 25.5 years. Male:female ratio was 1.8:1. Various symptoms including fever (100%), headache (75.3%), vomiting (55.6%), nausea (53.1%), and backache (30.9%) were observed among these patients. Thrombocytopenia (<100/10(9) platelets/L), and leucopenia (WBC count <4,000 × 10(9) cells/L) and hemoconcentration (hematocrit >45) were reported in 86.4, 69.1, and 67.9% of the patients, respectively. High alanine aminotransferase (ALT, >65 U/L) and aspartate aminotransferase (AST >37 U/L) were seen in 9.9 and 14.8% of the patients, respectively. There were five (6.1%) deaths, three of them had DHF and the other two patients had DSS.

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

    PubMed

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

    2014-07-01

    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.

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

    PubMed

    Choy, Milly M; Zhang, Summer L; Costa, Vivian V; Tan, Hwee Cheng; Horrevorts, Sophie; Ooi, Eng Eong

    2015-11-01

    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

  19. 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

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

    PubMed

    Choy, Milly M; Zhang, Summer L; Costa, Vivian V; Tan, Hwee Cheng; Horrevorts, Sophie; Ooi, Eng Eong

    2015-11-01

    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.

  1. Dengue and dengue hemorrhagic fever.

    PubMed

    Hayes, E B; Gubler, D J

    1992-04-01

    Hundreds of thousands of dengue cases are reported worldwide each year. Given the difficulty in obtaining full reporting, the actual number of human infections is probably much higher than the number reported. Dengue is usually a nonspecific febrile illness that resolves with supportive therapy but the clinical spectrum ranges from asymptomatic infection through severe hemorrhage and sudden fatal shock. The pathophysiology of the severe forms of dengue may be related to sequential infection with different serotypes, variations in virus virulence, interaction of the virus with environmental and host factors or a combination of these factors. Control of dengue at the present time is dependent on control of the principal vector mosquito, A. aegypti. Efforts to achieve such control are now focusing on community education and action towards eliminating this mosquito's breeding sites near human dwellings. Vaccine development continues, but at present the only way to avoid dengue in an area where it is endemic or epidemic is to use repellents and mosquito barriers. The movement of people to and from tropical areas makes dengue an important differential diagnosis in any patient with an acute illness and history of recent travel to tropical areas. Because of continued infestation of the southeastern United States with A. aegypti, indigenous transmission in the continental United States remains a public health concern.

  2. Laboratory diagnosis of acute dengue fever during the United Nations Mission in Haiti, 1995-1996.

    PubMed

    Rossi, C A; Drabick, J J; Gambel, J M; Sun, W; Lewis, T E; Henchal, E A

    1998-08-01

    We evaluated laboratory methods to confirm a clinical diagnosis of dengue. Acute sera were collected from personnel (n = 414) supporting the United Nations Mission in Haiti and presenting with febrile illness consistent with dengue fever or no apparent underlying cause. Dengue virus was recovered from 161 of 379 acute sera by inoculation into C6/36 cell culture. While 93 of 414 acute sera had detectable IgM antibodies, the IgM capture ELISA (MAC ELISA) had a sensitivity of only 13% compared with the virus isolation gold standard. If presumptive dengue fever cases were identified by both virus isolation and the presence of IgM, virus isolation and the MAC ELISA had clinical sensitivities of 69% and 40%, respectively. This study suggests that a combination of laboratory methods that target virus or subviral components as well as anti-viral IgM antibodies may be necessary for sensitive laboratory diagnosis with acute sera.

  3. Temporal patterns and forecast of dengue infection in Northeastern Thailand.

    PubMed

    Silawan, Tassanee; Singhasivanon, Pratap; Kaewkungwal, Jaranit; Nimmanitya, Suchitra; Suwonkerd, Wanapa

    2008-01-01

    This study aimed to determine temporal patterns and develop a forecasting model for dengue incidence in northeastern Thailand. Reported cases were obtained from the Thailand national surveillance system. The temporal patterns were displayed by plotting monthly rates, the seasonal-trend decomposition procedure based on loess (STL) was performed using R 2.2.1 software, and the trend was assessed using Poisson regression. The forecasting model for dengue incidence was performed in R 2.2.1 and Intercooled Stata 9.2 using the seasonal Autoregressive Integrated Moving Average (ARIMA) model. The model was evaluated by comparing predicted versus actual rates of dengue for 1996 to 2005 and used to forecast monthly rates during January to December 2006. The results reveal that epidemics occurred every two years, with approximately three years per epidemic, and that the next epidemic will take place in 2006 to 2008. It was found that if a month increased, the rate ratio for dengue infection decreased by a factor 0.9919 for overall region and 0.9776 to 0.9984 for individual provinces. The amplitude of the peak, which was evident in June or July, was 11.32 to 88.08 times greater than the rest of the year. The seasonal ARIMA (2, 1, 0) (0, 1, 1)12 model was model with the best fit for regionwide data of total dengue incidence whereas the models with the best fit varied by province. The forecasted regional monthly rates during January to December 2006 should range from 0.27 to 17.89 per 100,000 population. The peak for 2006 should be much higher than the peak for 2005. The highest peaks in 2006 should be in Loei, Buri Ram, Surin, Nakhon Phanom, and Ubon Ratchathani Provinces.

  4. Estimation of the Basic Reproductive Ratio for Dengue Fever at the Take-Off Period of Dengue Infection.

    PubMed

    Jafaruddin; Indratno, Sapto W; Nuraini, Nuning; Supriatna, Asep K; Soewono, Edy

    2015-01-01

    Estimating the basic reproductive ratio ℛ 0 of dengue fever has continued to be an ever-increasing challenge among epidemiologists. In this paper we propose two different constructions to estimate ℛ 0 which is derived from a dynamical system of host-vector dengue transmission model. The construction is based on the original assumption that in the early states of an epidemic the infected human compartment increases exponentially at the same rate as the infected mosquito compartment (previous work). In the first proposed construction, we modify previous works by assuming that the rates of infection for mosquito and human compartments might be different. In the second construction, we add an improvement by including more realistic conditions in which the dynamics of an infected human compartments are intervened by the dynamics of an infected mosquito compartment, and vice versa. We apply our construction to the real dengue epidemic data from SB Hospital, Bandung, Indonesia, during the period of outbreak Nov. 25, 2008-Dec. 2012. We also propose two scenarios to determine the take-off rate of infection at the beginning of a dengue epidemic for construction of the estimates of ℛ 0: scenario I from equation of new cases of dengue with respect to time (daily) and scenario II from equation of new cases of dengue with respect to cumulative number of new cases of dengue. The results show that our first construction of ℛ 0 accommodates the take-off rate differences between mosquitoes and humans. Our second construction of the ℛ 0 estimation takes into account the presence of infective mosquitoes in the early growth rate of infective humans and vice versa. We conclude that the second approach is more realistic, compared with our first approach and the previous work. PMID:26413140

  5. Estimation of the Basic Reproductive Ratio for Dengue Fever at the Take-Off Period of Dengue Infection.

    PubMed

    Jafaruddin; Indratno, Sapto W; Nuraini, Nuning; Supriatna, Asep K; Soewono, Edy

    2015-01-01

    Estimating the basic reproductive ratio ℛ 0 of dengue fever has continued to be an ever-increasing challenge among epidemiologists. In this paper we propose two different constructions to estimate ℛ 0 which is derived from a dynamical system of host-vector dengue transmission model. The construction is based on the original assumption that in the early states of an epidemic the infected human compartment increases exponentially at the same rate as the infected mosquito compartment (previous work). In the first proposed construction, we modify previous works by assuming that the rates of infection for mosquito and human compartments might be different. In the second construction, we add an improvement by including more realistic conditions in which the dynamics of an infected human compartments are intervened by the dynamics of an infected mosquito compartment, and vice versa. We apply our construction to the real dengue epidemic data from SB Hospital, Bandung, Indonesia, during the period of outbreak Nov. 25, 2008-Dec. 2012. We also propose two scenarios to determine the take-off rate of infection at the beginning of a dengue epidemic for construction of the estimates of ℛ 0: scenario I from equation of new cases of dengue with respect to time (daily) and scenario II from equation of new cases of dengue with respect to cumulative number of new cases of dengue. The results show that our first construction of ℛ 0 accommodates the take-off rate differences between mosquitoes and humans. Our second construction of the ℛ 0 estimation takes into account the presence of infective mosquitoes in the early growth rate of infective humans and vice versa. We conclude that the second approach is more realistic, compared with our first approach and the previous work.

  6. Preliminary study of dengue virus infection in Iran.

    PubMed

    Chinikar, Sadegh; Ghiasi, Seyed Mojtaba; Shah-Hosseini, Nariman; Mostafavi, Ehsan; Moradi, Maryam; Khakifirouz, Sahar; Rasi Varai, Fereshteh Sadat; Rafigh, Mahboubeh; Jalali, Tahmineh; Goya, Mohammad Mehdi; Shirzadi, Mohammad Reza; Zainali, Mohammad; Fooks, Anthony R

    2013-01-01

    Dengue fever is one of the most important arthropod-borne viral diseases of public health significance. It is endemic in most tropical and subtropical parts of the world, many of which are popular tourist destinations. The presence of dengue infection was examined in Iranian patients who were referred to the Arboviruses and Viral Haemorrhagic Fevers Laboratory of the Pasteur Institute of Iran and tested negative for Crimean-Congo Haemorrhagic Fever (CCHF) between 2000 and 2012. Serum samples from these patients were tested for the presence of specific IgG and IgM and viral nucleic acid in blood. Of the 300 sera tested, 15 (5%) were seropositive, and 3 (1%) were both serologically and PCR positive. Of the 15 seropositive cases, 8 (53.3%) had travelled to endemic areas including Malaysia (5, 62.5%), India (2, 25%) and Thailand (1, 12.5%). In contrast, 7 (46.7%) of the cases had not reported travelling abroad. Of these, six cases were from the Sistan and Baluchistan province in southeast Iran and neighbouring Pakistan. Travellers play a key role in the epidemiology of dengue infection in Iran and it is recommended that travellers to endemic areas take precautionary measures to avoid mosquito bites.

  7. Complement alternative pathway genetic variation and Dengue infection in the Thai population.

    PubMed

    Kraivong, R; Vasanawathana, S; Limpitikul, W; Malasit, P; Tangthawornchaikul, N; Botto, M; Screaton, G R; Mongkolsapaya, J; Pickering, M C

    2013-11-01

    Dengue disease is a mosquito-borne infection caused by Dengue virus. Infection may be asymptomatic or variably manifest as mild Dengue fever (DF) to the most severe form, Dengue haemorrhagic fever (DHF). Mechanisms that influence disease severity are not understood. Complement, an integral component of the immune system, is activated during Dengue infection and the degree of activation increases with disease severity. Activation of the complement alternative pathway is influenced by polymorphisms within activation (factor B rs12614/rs641153, C3 rs2230199) and regulatory [complement factor H (CFH) rs800292] proteins, collectively termed a complotype. Here, we tested the hypothesis that the complotype influences disease severity during secondary Dengue infection. In addition to the complotype, we also assessed two other disease-associated CFH polymorphisms (rs1061170, rs3753394) and a structural polymorphism within the CFH protein family. We did not detect any significant association between the examined polymorphisms and Dengue infection severity in the Thai population. However, the minor allele frequencies of the factor B and C3 polymorphisms were less than 10%, so our study was not sufficiently powered to detect an association at these loci. We were also unable to detect a direct interaction between CFH and Dengue NS1 using both recombinant NS1 and DV2-infected culture supernatants. We conclude that the complotype does not influence secondary Dengue infection severity in the Thai population.

  8. Early Dengue Virus Infection in Human Skin: A Cycle of Inflammation and Infectivity.

    PubMed

    Ivory, Matthew O; Birchall, James C; Piguet, Vincent

    2015-07-01

    Early events during dengue virus (DENV) infection remain poorly understood. In this issue, Schaeffer and colleagues employ ex vivo human skin cells to investigate viral infection. They show that skin-resident immune cells are infected by DENV and that their infectability is increased in the inflammatory skin conditions (especially those in which IL-4 is released) that accompany the mosquito bites transmitting the virus.

  9. 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.

  10. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity.

    PubMed

    Koraka, Penelopie; Murgue, Bernadette; Deparis, Xavier; Setiati, Tatty E; Suharti, Catarina; van Gorp, Eric C M; Hack, C E; Osterhaus, Albert D M E; Groen, Jan

    2003-05-01

    The kinetics of total and dengue virus-specific immunoglobulin E (IgE) were studied in serial serum samples obtained from 168 patients, 41 of whom suffered from primary dengue virus infection and 127 suffered from secondary dengue virus infection. Seventy-one patients were classified as dengue fever, 30 as dengue hemorrhagic fever, and 67 as dengue shock syndrome. A control group included single serum samples from patients with a herpes virus infection (n = 14), non-dengue febrile patients (n = 10), and healthy blood donors (n = 10). Patients with dengue virus infection had higher levels of total and dengue virus-specific IgE than non-dengue patients (P < 0.05). Patients with secondary dengue virus infections had not significantly increased levels of both total and dengue virus-specific IgE in the acute phase of disease compared to patients with primary dengue virus infections. Dengue virus-specific IgE was significantly higher in dengue hemorrhagic fever and/or dengue shock syndrome patients compared to dengue fever and non-dengue patients (P < 0.05). In conclusion, this study showed elevated total and dengue virus-specific IgE serum antibody levels in the acute stage of disease. Therefore, measurement of both total and dengue virus-specific IgE serum antibodies can be used as an additional prognostic marker in the development of severe complications in dengue virus infections. In addition, the presence and increase of dengue virus-specific IgE serum antibodies in patients with dengue virus infections is suggestive of the pathogenetic role that IgE may play in the hemostatic disorders observed in dengue hemorrhagic fever and dengue shock syndrome.

  11. Acute cytomegalovirus (CMV) infection

    MedlinePlus

    CMV mononucleosis; Cytomegalovirus (CMV) ... Infection with cytomegalovirus (CMV) is very common. The infection is spread by: Blood transfusions Organ transplants Respiratory droplets Saliva Sexual contact ...

  12. Appendicular mass complicating acute appendicitis in a patient with dengue fever.

    PubMed

    Low, Y N; Cheong, B M K

    2016-04-01

    Abdominal pain with dengue fever can be a diagnostic challenge. Typically, pain is localised to the epigastric region or associated with hepatomegaly. Patients can also present with acute abdomen. We report a case of a girl with dengue fever and right iliac fossa pain. The diagnosis of acute appendicitis was made only after four days of admission. An appendicular mass and a perforated appendix was noted during appendectomy. The patient recovered subsequently. Features suggestive of acute appendicitis are persistent right iliac fossa pain, localised peritonism, persistent fever and leucocytosis. Repeated clinical assessment is important to avoid missing a concurrent diagnosis like acute appendicitis. PMID:27326951

  13. Dengue virus infections in Nigeria: a survey for antibodies in monkeys and humans.

    PubMed

    Fagbami, A H; Monath, T P; Fabiyi, A

    1977-01-01

    A retrospective serological survey for dengue immunity was conducted in Nigeria to determine the prevalence of infection in man and non-human primates. Preliminary haemagglutination-inhibition (HI) tests revealed that 63% of persons tested had HI antibodies against one or more of the following flaviviruses: dengue type 1, yellow fever, West Nile and Wesselsbron. Parallel HI and neutralization (N) tests on 179 human sera showed that six of 20 sera (30%) negative for flavivirus HI antibody contained dengue N antibody. This finding emphasized the advantage of the N test over HI in screening for dengue virus immunity. Neutralization tests performed on 1,816 human sera from different geographical locations in Nigeria showed that 45% of Nigerians were immune to dengue type 2 virus. The percentage of immunity in adults aged 20 years and older (51%) was significantly higher than in children (37%) (P less than 0-01). In all four ecological zones sampled, the highest percentage of dengue N antibody was observed in the derived Savannah zone (63%) followed by the rain forest zone (42%). The Southern Guinea savannah and plateau zones had lower percentages of dengue-immune persons. There was a higher prevalence of antibodies in urban (48%) than in rural communities (37%). Tests on dengue-immune sera showed that 35% of such sera contained N antibodies to dengue only or to dengue and one other virus. Therefore, dengue immunity cannot be explained by heterologous cross reactions within the flavivirus group. In addition, evidence of dengue infection was found in monkeys and galagos. 48% of monkeys and 25% of galagos contained dengue N antibody. The presence of specific dengue N antibodies in a few sera suggests that the occurrence of a forest cycle of dengue is possible in Nigeria.

  14. 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.

  15. 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

  16. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection.

    PubMed

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

    2016-09-01

    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

  17. A genomics approach to understanding host response during dengue infection.

    PubMed

    Hibberd, Martin L; Ling, Ling; Tolfvenstam, Thomas; Mitchell, Wayne; Wong, Chris; Kuznetsov, Vladimir A; George, Joshy; Ong, Swee-Hoe; Ruan, Yijun; Wei, Chia L; Gu, Feng; Fink, Joshua; Yip, Andy; Liu, Wei; Schreiber, Mark; Vasudevan, Subhash G

    2006-01-01

    Dengue infection results in a wide clinical spectrum, ranging from asymptomatic, through fever (DF), to the life threatening complications haemorrhagic fever (DHF) and shock syndrome (DSS). Although we now understand that factors such as repeat infections and the type or magnitude of the host response are important in determining severity, the mechanisms of these actions remain largely unknown. Understanding this host-pathogen interaction may enable outcome prediction and new therapy options. Developments in biology now allow a 'systems approach' to be applied to this problem, utilizing whole genomes of both human and virus, in vitro and in vivo to enable a more complete picture of their interplay to be built up. We have developed a chip-based approach to viral sequencing, to increase efficiency and enable large numbers ofgenomes to be completed, together with a web-based interpretation tool. We have also applied human whole genome expression arrays (24000 genes) to characterize the types of host response made to infection and plan to investigate the role of host variation using human whole genome genetic association studies in the future. These technologies have identified novel host pathways involved in viral replication in vitro, and also host immune responses, such as the interferon signalling pathway, that are influenced by viral sequence. This data will be further refined through interlinking with similar data obtained from a large study of dengue patients, initiated in Singapore, that is able to look at the early host response to infection.

  18. Infections with two dengue viruses in Greece in the 20th century. Did dengue hemorrhagic fever occur in the 1928 epidemic?

    PubMed

    Papaevangelou, G; Halstead, S B

    1977-03-01

    From contemporary clinical accounts we hypothesized that the 1928 dengue epidemic in Greece may have been an earlier occurrence of dengue hemorrhagic fiver/dengue shock syndrome (DHF/DSS). To study the possibility that two different dengue viruses may have been involved, serums from 62 Athenians alive during the epidemic were examined for dengue antibodies; 73 per cent showed evidence of prior dengue infection. Monotypic neutralizing antibodies were found to two different dengue viruses, types 1 and 2. A large proportion of the sampled population had evidence of two or more past dengue infections. Since there is no evidence that dengue viruses have been transmitted in Greece since 1928, during the epidemic a very large number of persons immune to one dengue type must have acquired infections with a secon type. The virological criteria for secondary infection DHF/DSS are thus satisfied. Although DHF/DSS is currently restricted to Asia and the Pacific, the Greek oubreak suggests a biological potential for fatal consequences of dengue infections in Caucasians, particularly the elderly.

  19. Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections.

    PubMed

    Ben-Shachar, Rotem; Koelle, Katia

    2015-02-01

    In recent years, the within-host viral dynamics of dengue infections have been increasingly characterized, and the relationship between aspects of these dynamics and the manifestation of severe disease has been increasingly probed. Despite this progress, there are few mathematical models of within-host dengue dynamics, and the ones that exist focus primarily on the general role of immune cells in the clearance of infected cells, while neglecting other components of the immune response in limiting viraemia. Here, by considering a suite of mathematical within-host dengue models of increasing complexity, we aim to isolate the critical components of the innate and the adaptive immune response that suffice in the reproduction of several well-characterized features of primary and secondary dengue infections. By building up from a simple target cell limited model, we show that only the innate immune response is needed to recover the characteristic features of a primary symptomatic dengue infection, while a higher rate of viral infectivity (indicative of antibody-dependent enhancement) and infected cell clearance by T cells are further needed to recover the characteristic features of a secondary dengue infection. We show that these minimal models can reproduce the increased risk of disease associated with secondary heterologous infections that arises as a result of a cytokine storm, and, further, that they are consistent with virological indicators that predict the onset of severe disease, such as the magnitude of peak viraemia, time to peak viral load, and viral clearance rate. Finally, we show that the effectiveness of these virological indicators to predict the onset of severe disease depends on the contribution of T cells in fuelling the cytokine storm.

  20. Spectrum of Maternofetal Outcomes during Dengue Infection in Pregnancy: An Insight.

    PubMed

    Sharma, Swati; Jain, Sandhya; Rajaram, Shalini

    2016-01-01

    Dengue is a vector transmitted viral infection; tropical and subtropical countries see outbreaks of dengue each year. There is a paucity of literature on effects of dengue infection on pregnancy outcome and this prompted us to undertake a study for better understanding of pregnancy implications with dengue infection. Pregnant women admitted during the seasonal outbreak of dengue between September 2015 and October 2015 were studied and maternal and fetal outcomes in sixteen NS1Ag positive women were analysed. Out of sixteen women diagnosed with dengue fever, three had dengue shock syndrome (DSS) and eight had dengue haemorrhagic fever (DHF). The most common obstetric complication seen in 43% of the cases was oligohydramnios. Bleeding manifestations occurred in seven women and there were three maternal deaths. Perinatal complications included three intrauterine deaths, six nursery admissions, and one neonatal death. Thus dengue infection was associated with high maternal and perinatal mortality. In view of poor obstetric outcomes, this viral infection warrants early admission and prompt management.

  1. Spectrum of Maternofetal Outcomes during Dengue Infection in Pregnancy: An Insight.

    PubMed

    Sharma, Swati; Jain, Sandhya; Rajaram, Shalini

    2016-01-01

    Dengue is a vector transmitted viral infection; tropical and subtropical countries see outbreaks of dengue each year. There is a paucity of literature on effects of dengue infection on pregnancy outcome and this prompted us to undertake a study for better understanding of pregnancy implications with dengue infection. Pregnant women admitted during the seasonal outbreak of dengue between September 2015 and October 2015 were studied and maternal and fetal outcomes in sixteen NS1Ag positive women were analysed. Out of sixteen women diagnosed with dengue fever, three had dengue shock syndrome (DSS) and eight had dengue haemorrhagic fever (DHF). The most common obstetric complication seen in 43% of the cases was oligohydramnios. Bleeding manifestations occurred in seven women and there were three maternal deaths. Perinatal complications included three intrauterine deaths, six nursery admissions, and one neonatal death. Thus dengue infection was associated with high maternal and perinatal mortality. In view of poor obstetric outcomes, this viral infection warrants early admission and prompt management. PMID:27069349

  2. 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.

  3. C1q binding to dengue virus decreases levels of infection and inflammatory molecules transcription in THP-1 cells.

    PubMed

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

    2014-01-22

    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.

  4. Placental passage of antibodies to Dengue virus in persons living in a region of hyperendemic Dengue virus infection.

    PubMed

    Ventura, A K; Ehrenkranz, N J; Rosenthal, D

    1975-05-01

    Maternal and umbilical cord levels of antibodies to dengue 2 and 3 viruses were compared in 54 matched pairs of specimens from subjects in the Dominican Republic. Dengue infection appeared to be hyperendemic; pregnant women experienced a 6% weekly infection rate. Titers of antibody to dengue 2 and 3 viruses were considerably higher in cord sera than in maternal sera (P smaller than 0.001 and P smaller 0.01, respectively), especially when maternal levels were low. When maternal and cord sera were compared at equal titers of dengue 2 virus, heterotypic antibodies to dengue 1 and St. Louis encephalitis viruses were higher in the cord. These findings could not be directly related to the higher levels of IgG found in cord sera or to the presence of elevated concentrations of IgM. It is concluded that antibody with increased cross-reactivity preferentially crosses the placenta. The presence of such cross-reactive antibody does not appear to sensitize infants to dengue hemorrhagic fever/shock syndrome.

  5. Drug repurposing of minocycline against dengue virus infection.

    PubMed

    Leela, Shilpa Lekshmi; Srisawat, Chatchawan; Sreekanth, Gopinathan Pillai; Noisakran, Sansanee; Yenchitsomanus, Pa-Thai; Limjindaporn, Thawornchai

    2016-09-01

    Dengue virus infection is one of the most common arthropod-borne viral diseases. A complex interplay between host and viral factors contributes to the severity of infection. The antiviral effects of three antibiotics, lomefloxacin, netilmicin, and minocycline, were examined in this study, and minocycline was found to be a promising drug. This antiviral effect was confirmed in all four serotypes of the virus. The effects of minocycline at various stages of the viral life cycle, such as during viral RNA synthesis, intracellular envelope protein expression, and the production of infectious virions, were examined and found to be significantly reduced by minocycline treatment. Minocycline also modulated host factors, including the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2). The transcription of antiviral genes, including 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase 3 (OAS3), and interferon α (IFNA), was upregulated by minocycline treatment. Therefore, the antiviral activity of minocycline may have a potential clinical use against Dengue virus infection. PMID:27396621

  6. 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.

  7. 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... ...

  8. 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.

  9. Outbreak of dengue fever in Palau, Western Pacific: risk factors for infection.

    PubMed

    Ashford, David A; Savage, Harry M; Hajjeh, Rana A; McReady, Jill; Bartholomew, David M; Spiegel, Richard A; Vorndam, Vance; Clark, Gary G; Gubler, Duane G

    2003-08-01

    Between January and June 1995, an outbreak of dengue fever occurred in Palau, an island nation of 32,000 inhabitants in the Western Pacific. To determine the magnitude of this outbreak and to determine modifiable risk factors to guide control strategies, we established active surveillance at the national hospital and private clinics, reviewed available clinical records, and conducted serologic and entomologic surveys. Between January 1 and July 1, 1995, 817 case-patients with acute febrile illness with body or joint aches and one of the following: headache, rash, nausea, vomiting, or hemorrhagic manifestations presented to health facilities in Palau. The epidemic peaked in the second week of April 1995. Of 338 case-patients tested, 254 (75%) had positive serologic results by an IgM capture enzyme-linked immunosorbent assay. Dengue 4 virus was isolated from 78 (51%) of 154 serum samples tested. Blood samples collected during a cross-sectional survey were tested for IgM antibody and yielded an attack ratio of 27% (95% confidence interval = 23-31%). Potential vectors included the introduced species Aedes aegypti and Ae. albopictus, and the native species Ae. hensilli. Significant risk factors (P < or = 0.05) for infection included age < 20 years, the presence of food or water pans for animals on the property, taro farming, the presence of Ae. aegypti on the property, and presence of Ae. scutellaris group mosquitoes (Ae. Hensilli, Ae. albopictus, and a native species). This was the first outbreak of dengue 4 virus in the Western Pacific, and the first documented epidemic of dengue in Palau since 1988.

  10. Short report: immune response and occurrence of dengue infection in thai children three to eight years after vaccination with live attenuated tetravalent dengue vaccine.

    PubMed

    Chanthavanich, Pornthep; Luxemburger, Christine; Sirivichayakul, Chukiat; Lapphra, Keswadee; Pengsaa, Krisana; Yoksan, Sutee; Sabchareon, Arunee; Lang, Jean

    2006-07-01

    From 1992 to 1997, 140 Thai children 4-15 years of age received an investigational live attenuated tetravalent dengue vaccine (LATDV). These children were contacted 3-8 years later in 2001 to assess humoral immunity and investigate whether they were subsequently at higher risk of developing severe dengue. One hundred thirteen were successfully contacted and participated in this retrospective cohort study with two age- and address-matched controls per vaccinee. The number of vaccinated subjects with neutralizing antibodies increased compared with 3-8 years earlier, which was probably due to subsequent wild-type dengue infections. There were no excess hospitalizations for clinically suspected dengue fever (DF) or dengue hemorrhagic fever (DHF) in vaccinees (one with DF and three with DHF) compared with controls (14 with DHF). Results suggest that preexisting dengue antibodies induced by LATDV do not enhance dengue illness, and the use of the vaccine in a dengue-endemic area is safe.

  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. 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.

  13. 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. PMID:27366770

  14. Frequency and Clinical Manifestations of Dengue in Urban Medellin, Colombia

    PubMed Central

    Restrepo, Berta Nelly; Beatty, Mark E.; Goez, Yenny; Ramirez, Ruth E.; Letson, G. William; Diaz, Francisco J.; Piedrahita, Leidy Diana; Osorio, Jorge E.

    2014-01-01

    A dengue fever surveillance study was conducted at three medical facilities located in the low-income district of San Javier in Medellin, Colombia. During March 2008 to 2009, 781 patients with fever regardless of chief complaint were recruited for acute dengue virus infection testing. Of the 781 tested, 73 (9.3%) were positive for dengue infection. Serotypes DENV-2 (77%) and -3 (23%) were detected by PCR. One patient met the diagnostic criteria for dengue hemorrhagic fever. Only 3 out of 73 (4.1%) febrile subjects testing positive for dengue infection were diagnosed with dengue fever by the treating physician. This study confirms dengue virus as an important cause of acute febrile illness in Medellin, Colombia, but it is difficult to diagnose without dengue diagnostic testing. PMID:24987421

  15. 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.

  16. 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.

  17. Dengue vaccine.

    PubMed

    Simasathien, Sriluck; Watanaveeradej, Veerachai

    2005-11-01

    Dengue is an expanding health problem. About two-fifths of the world population are at risk for acquiring dengue with 50-100 million cases of acute febrile illness yearly including about 500,000 cases of DHF/DSS. No antiviral drugs active against the flavivirus exist. Attempts to control mosquito vector has been largely unsuccessful. Vaccination remains the most hopeful preventive measure. Dengue vaccine has been in development for more than 30 years, yet none has been licensed. The fact that enhancing antibody from previous infection and high level of T cell activation during secondary infection contribute to immunopathology of DHF, the vaccine must be able to induce protective response to four dengue serotypes simultaneously. Inactivated vaccine is safe but needs a repeated booster thus, development is delayed. Tetravalent live attenuated vaccine and chimeric vaccine using yellow fever or dengue viruses as a backbone are being carried out in human trials. DNA vaccine and subunit vaccine are being carried out in animal trials.

  18. Determinants of dengue 2 infection among residents of Charters Towers, Queensland, Australia.

    PubMed

    McBride, W J; Mullner, H; Muller, R; Labrooy, J; Wronski, I

    1998-12-01

    Dengue fever is caused by one of the four serotypes of the dengue virus and is transmitted by the urban mosquito Aedes aegypti. In 1993, the city of Charters Towers in the tropical north of Australia experienced an epidemic caused by the dengue 2 virus. A cross-sectional sample of 1,000 people was assessed for determinants of recent symptomatic dengue infection. After exclusion of people with prior exposure to dengue 2, a study group of 797 persons, including 196 patients with recent infection, were evaluated. Stepwise logistic regression analysis identified four determinants of infection: the presence of a case of dengue fever within two residential blocks (odds ratio (OR) = 3.61, 95% confidence interval (CI) 2.56-5.10), house screening (OR = 0.60, 95% CI 0.40-0.89), the presence of a water tank within two residential blocks (OR = 1.51, 95% CI 1.02-2.22), and the use of knockdown insecticide (OR = 1.75, 95% CI 1.22-2.51). Classification and Regression Tree analysis identified a group of 152 individuals in whom the prevalence of dengue infection was 50%. These people lived within two blocks of a suspected dengue fever case, did not have house screening, and used knockdown sprays. If dengue had not occurred within two residential blocks, there were no additional factors that significantly influenced the prevalence of dengue fever. Control of dengue epidemics should involve attempts to geographically contain the spread of infection, use of house screening, and the removal of mosquito breeding sites such as water tanks.

  19. 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.

  20. 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

    2016-06-01

    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.

  1. 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

    2016-06-01

    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. PMID:27277216

  2. 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.

  3. Burden of dengue infection and disease in a pediatric cohort in urban Sri Lanka.

    PubMed

    Tissera, Hasitha; Amarasinghe, Ananda; De Silva, Aruna Dharshan; Kariyawasam, Pradeep; Corbett, Kizzmekia S; Katzelnick, Leah; Tam, Clarence; Letson, G William; Margolis, Harold S; de Silva, Aravinda M

    2014-07-01

    Dengue is the most significant arthropod-borne viral infection of humans. Persons infected with dengue viruses (DENV) have subclinical or clinically apparent infections ranging from undifferentiated fever to dengue hemorrhagic fever/shock syndrome. Although recent studies estimated that the Indian subcontinent has the greatest burden of DENV infection and disease worldwide, we do not have reliable, population-based estimates of the incidence of infection and disease in this region. The goal of this study was to follow-up a cohort of 800 children living in a heavily urbanized area of Colombo, Sri Lanka to obtain accurate estimates of the incidence of DENV infection and disease. Annual blood samples were obtained from all children to estimate dengue seroprevalence at enrollment and to identify children exposed to new DENV infections during the study year. Blood was also obtained from any child in whom fever developed over the course of the study year to identify clinically apparent DENV infections. At enrollment, dengue seroprevalence was 53.07%, which indicated high transmission in this population. Over the study year, the incidence of DENV infection and disease were 8.39 (95% confidence interval = 6.56-10.53) and 3.38 (95% confidence interval = 2.24-4.88), respectively, per 100 children per year. The ratio of clinically inapparent to apparent infections was 1.48. These results will be useful for obtaining more accurate estimates of the burden of dengue in the region and for making decisions about testing and introduction of vaccines.

  4. Co-infection of dengue fever and hepatitis A in a Russian traveler.

    PubMed

    Volchkova, Elena; Umbetova, Karina; Belaia, Olga; Sviridova, Maria; Dmitrieva, Ludmila; Arutyunova, Daria; Chernishov, Dmitriy; Karan, Ludmila

    2016-01-01

    We report a hepatitis A (HAV) and dengue virus (DENV) co-infection in Russian man who had been traveling to Dominican Republic. At admission to the hospital hemorrhagic and jaundice symptoms were observed in patient. PCR tests of blood serum and urine revealed RNA dengue virus type 3, HAV RNA, anti-HAV-IgM. PMID:27516967

  5. Dengue virus infections in travellers returning from Benin to France, July-August 2010.

    PubMed

    Gautret, P; Botelho-Nevers, E; Charrel, R N; Parola, P

    2010-09-01

    In July and August 2010, two cases of dengue fever were diagnosed in travellers returning from Benin to France. These two cases exemplify that dengue fever should be considered in febrile travellers, even those returning from areas where the infection is not usual.

  6. Co-infection of dengue fever and hepatitis A in a Russian traveler.

    PubMed

    Volchkova, Elena; Umbetova, Karina; Belaia, Olga; Sviridova, Maria; Dmitrieva, Ludmila; Arutyunova, Daria; Chernishov, Dmitriy; Karan, Ludmila

    2016-01-01

    We report a hepatitis A (HAV) and dengue virus (DENV) co-infection in Russian man who had been traveling to Dominican Republic. At admission to the hospital hemorrhagic and jaundice symptoms were observed in patient. PCR tests of blood serum and urine revealed RNA dengue virus type 3, HAV RNA, anti-HAV-IgM.

  7. 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.

  8. Two Case Reports on Thalamic and Basal Ganglia Involvement in Children with Dengue Fever

    PubMed Central

    Adhikari, Lihini; Wijesekera, Saraji; Wijayawardena, Maheshaka; Chandrasiri, Suchithra

    2016-01-01

    There have been increasing numbers of case reports of dengue infection with unusual manifestations. Such unusual manifestations including acute liver failure and encephalopathy could be manifested even in the absence of significant plasma leakage. Further, severe organ involvement including nervous system involvement indicates severe dengue infection. However, neurological manifestations of dengue fever are rare. This is the first case report of dengue infection with thalamic and basal ganglia involvement in Sri Lanka. PMID:27478661

  9. Two Case Reports on Thalamic and Basal Ganglia Involvement in Children with Dengue Fever.

    PubMed

    Liyanage, Guwani; Adhikari, Lihini; Wijesekera, Saraji; Wijayawardena, Maheshaka; Chandrasiri, Suchithra

    2016-01-01

    There have been increasing numbers of case reports of dengue infection with unusual manifestations. Such unusual manifestations including acute liver failure and encephalopathy could be manifested even in the absence of significant plasma leakage. Further, severe organ involvement including nervous system involvement indicates severe dengue infection. However, neurological manifestations of dengue fever are rare. This is the first case report of dengue infection with thalamic and basal ganglia involvement in Sri Lanka. PMID:27478661

  10. A Hospital Based Serosurveillance Study of Dengue Infection in Jaipur (Rajasthan) , India

    PubMed Central

    Sood, Smita

    2013-01-01

    Background: Dengue has been known to be endemic in India for over two centuries. There is a need to assess the magnitude of dengue virus establishment in the state of Rajasthan. A surveillance study was conducted to analyze dengue seropositivity among patients with clinical suspicion of dengue fever like illness, who presented to or were admitted at a tertiary care private hospital at Jaipur. Methods: Serum samples from 2169 suspected dengue cases (1356 males and 813 females) were received in the Serology lab over the four year study period (2008-2011). The samples were subjected to a rapid immuno-chromatography assay with differential detection of IgM and IgG antibodies. A primary dengue infection was defined by a positive IgM band and a negative IgG band, whereas a secondary infection was defined by a positive Ig G band with or without an IgM band. Result: Among the 2169 patients who were screened; 18.99% (412) were dengue specific IgM positive cases. 64. 49% (1399) cases were negative for dengue specific antibodies, 5.67% (123) were primary dengue cases, and 23.51% (510) were total secondary dengue cases. During the study period, the Dengue IgM seropositivity was highest in the year 2009 and was lowest in the year 2011. Most of the cases occurred in the post-monsoon season, with a peak in the month of October, each year. Conclusion: A detailed and continuous epidemiological surveillance is required, for monitoring the incrusion and spread of dengue viruses. This will help in undertaking and implementing effective control and management strategies. PMID:24179897

  11. TNF and LTA gene, allele, and extended HLA haplotype associations with severe dengue virus infection in ethnic Thais.

    PubMed

    Vejbaesya, Sasijit; Luangtrakool, Panpimon; Luangtrakool, Komon; Kalayanarooj, Siripen; Vaughn, David W; Endy, Timothy P; Mammen, Mammen P; Green, Sharone; Libraty, Daniel H; Ennis, Francis A; Rothman, Alan L; Stephens, Henry A F

    2009-05-15

    Severe dengue virus (DENV) infection is characterized by a cascade of cytokine production, including the production of tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha (LT-alpha). We have analyzed a variety of polymorphisms in the TNF and LTA genes of 435 ethnic Thais who had subclinical DENV infection, primary or secondary dengue fever (DF), or primary or secondary dengue hemorrhagic fever (DHF). The TNF -238A polymorphism marking the TNF-4,LTA-3 haplotype occurred in a significantly greater number of patients with secondary DHF (20 [15.2%] of 132) than patients with secondary DF (7 [4.1%] of 169) (P < .001; P corrected by use of Bonferroni adjustment, .022; odds ratio, 4.13 [95% confidence interval, 1.59-11.17]). In a subset of patients, the LTA-3 haplotype was associated with in vivo intracellular production of LT-alpha and TNF-alpha during the acute viremic phase of infection. Two extended human major histocompatibility complex (MHC) haplotypes containing TNF-4 and LTA-3, together with HLA-B48, HLA-B57, and HLA-DPB1*0501, were detected only in patients with secondary DHF. These observations indicate that polymorphism in functionally distinct MHC-encoded proteins contributes to the risk of developing severe secondary DENV infection and warrants further investigation.

  12. Unique impacts of HBV co-infection on clinical and laboratory findings in a recent dengue outbreak in China.

    PubMed

    Tang, Yangbo; Kou, Zhihua; Tang, Xiaoping; Zhang, Fuchun; Yao, Xian; Liu, Shengyong; Jin, Xia

    2008-08-01

    High prevalence of hepatitis B virus (HBV) infection in China offers a unique setting to examine HBV's influence on the presentation of dengue fever. In 398 patients admitted for suspected dengue fever, 89% (353/398) were positive for dengue IgM antibodies. Among dengue-infected patients, 8% (29/353) had chronic HBV co-infection. Only dengue virus serotype 1 was identified by virus isolation and reverse transcriptase-polymerase chain reaction assays. No case of dengue hemorrhagic fever/dengue shock syndrome was diagnosed. In addition to routine clinical tests, interleukin 2 (IL-2), IL-4, IL-6, IL-10, interferon gamma (IFNgamma), and tumor necrosis factor alpha (TNFalpha) levels were measured in the sera of 95% (334/353) of dengue-infected subjects as well as controls. Surprisingly, HBV/dengue co-infected patients made less IL-6 (P < 0.05) and TNFalpha (P < 0.05) than patients with only dengue infection. Similar levels of IL-4, IL-10, and IFNgamma were found in both groups. Thus, HBV co-infection seems to alter the cytokine production pattern when patients contract dengue infection.

  13. Diabetes Mellitus Increases Severity of Thrombocytopenia in Dengue-Infected Patients

    PubMed Central

    Chen, Chung-Yuan; Lee, Mei-Yueh; Lin, Kun-Der; Hsu, Wei-Hao; Lee, Yaun-Jinn; Hsiao, Pi-Jung; Shin, Shyi-Jang

    2015-01-01

    Background: Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. Methods: We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Results: Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54 ± 51.69 vs. 86.58 ± 63.4 (p ≤ 0.001), 43.98 ± 44.09 vs. 64.52 ± 45.06 (p = 0.002), 43.86 ± 35.75 vs. 62.72 ± 51.2 (p = 0.012)). Diabetes mellitus, death, dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF) and increased glutamic-pyruvate transaminase (GPT) levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of −13.981 (95% confidence interval (CI) −27.587, −0.374), −26.847 (95% CI −37.562, −16.132), and 0.054 (95% CI 0.015, 0.094) respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of −2.947 (p = 0.004), 2.801 (p = 0.005), and −3.568 (p ≤ 0.001), respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in

  14. Association between Nutritional Status and Severity of Dengue Infection in Children in El Salvador

    PubMed Central

    Marón, Gabriela M.; Clará, A. Wilfrido; Diddle, John Wesley; Pleités, Ernesto B.; Miller, Laura; MacDonald, Gene; Adderson, Elisabeth E.

    2010-01-01

    Clinical observations and some studies suggest that dengue virus infection is more severe among children with better nutritional status. We examined the nutritional status of children in El Salvador and its relationship between this and the severity of dengue infection. Z-scores for weight-for-age, height-for-age, and body mass index (BMI)-for-age of children with dengue fever (66), dengue hemorrhagic fever (62), and healthy controls (74) were compared. There were no differences in weight-for-age or BMI-for-age Z-scores between the three groups. Children with dengue fever had a greater height-for-age than healthy controls but no significant differences in rates of stunting. There was no difference in height between children with dengue fever and dengue hemorrhagic fever. Excess nutrition does not appear to be a risk factor for severe forms of dengue infection in El Salvador, nor does malnutrition appear to be predictive of good outcomes. PMID:20134012

  15. High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells

    PubMed Central

    Chiu, Han-Chen; Hannemann, Holger; Heesom, Kate J.; Matthews, David A.; Davidson, Andrew D.

    2014-01-01

    Disease caused by dengue virus is a global health concern with up to 390 million individuals infected annually worldwide. There are no vaccines or antiviral compounds available to either prevent or treat dengue disease which may be fatal. To increase our understanding of the interaction of dengue virus with the host cell, we analyzed changes in the proteome of human A549 cells in response to dengue virus type 2 infection using stable isotope labelling in cell culture (SILAC) in combination with high-throughput mass spectrometry (MS). Mock and infected A549 cells were fractionated into nuclear and cytoplasmic extracts before analysis to identify proteins that redistribute between cellular compartments during infection and reduce the complexity of the analysis. We identified and quantified 3098 and 2115 proteins in the cytoplasmic and nuclear fractions respectively. Proteins that showed a significant alteration in amount during infection were examined using gene enrichment, pathway and network analysis tools. The analyses revealed that dengue virus infection modulated the amounts of proteins involved in the interferon and unfolded protein responses, lipid metabolism and the cell cycle. The SILAC-MS results were validated for a select number of proteins over a time course of infection by Western blotting and immunofluorescence microscopy. Our study demonstrates for the first time the power of SILAC-MS for identifying and quantifying novel changes in cellular protein amounts in response to dengue virus infection. PMID:24671231

  16. 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.

  17. 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

  18. Predictors of hospital stay and mortality in dengue virus infection-experience from Aga Khan University Hospital Pakistan

    PubMed Central

    2014-01-01

    Background Dengue virus infection (DVI) is very common infection. There is scarcity of data on factor associated with increased hospital stay and mortality in dengue virus infection (DVI). This study was done to know about factors associated with increased hospital stay and mortality in patients admitted with DVI. Results Out of 532 patients, two third (72.6%) had stay ≤3 days while one third (27.4%) had stay greater than 3 days. The mean length of hospital stay was 3.46 ± 3.45 days. Factors associated with increased hospital stay (>3 days) included AKI (acute kidney injury) (Odd ratio 2.98; 95% CI 1.66-5.34), prolonged prothrombin time (Odd ratio 2.03; 95% CI 1.07-3.84), prolonged activated partial thromboplastin time (aPTT) (Odd ratio 1.80; CI 95% 1.15-2.83) and increased age of > 41.10 years (Odd ratio 1.03; CI 95% 1.01-1.04).Mortality was 1.5%. High mortality was found in those with AKI (P <0.01), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) (P <0.001), respiratory failure (P0.01), prolong PT (P 0.001), prolong aPTT (P0.01) and increased hospital stay (P0.04). Conclusion Increasing age, coagulopathy and acute kidney injury in patients with DVI is associated with increased hospital stay. Morality was more in patients with AKI, DHF and DSS, respiratory failure, coagulopathy and these patients had more prolonged hospitalization. PMID:25064632

  19. Incidence of Dengue Virus Infection in School-Aged Children in Puerto Rico: A Prospective Seroepidemiologic Study

    PubMed Central

    Argüello, D. Fermín; Tomashek, Kay M.; Quiñones, Luz; Beltran, Manuela; Acosta, Luz; Santiago, Luis M.; Biggerstaff, Brad J.; Garcia-Rivera, Enid J.; Sun, Wellington; Pollissard-Gadroy, Laurence; Luxemburger, Christine; Hunsperger, Elizabeth

    2015-01-01

    Dengue is a potentially fatal acute febrile illness caused by the mosquito-borne dengue viruses (DENV-1 to -4). To estimate DENV seroincidence in school-aged children, a 1-year prospective cohort study was conducted in Patillas, Puerto Rico; 10- to 18-year-olds (N = 345) were randomly selected from 13 public schools. At enrollment, 49.8% of the entire cohort had DENV immunoglobulin G (IgG) anti-DENV antibodies, and there were individuals with neutralizing antibodies specific to each of the four DENV. The mean age of participants with incident DENV infection was 13.4 years. The 1-year seroincidence rate was 5.6%, and 61.1% of infections were inapparent. Having IgG anti-DENV at enrollment was associated with seroincidence (risk ratio = 6.8). Acute febrile illnesses during the study period were captured by a fever diary and an enhanced and passive surveillance system in the municipios of Patillas and Guayama. In summary, at enrollment, nearly one-half of the participants had a prior DENV infection, with the highest incidence in the 10- to 11-year-olds, of which most were inapparent infections, and symptomatic infections were considered mild. PMID:25646256

  20. Incidence of dengue virus infection in school-aged children in Puerto Rico: a prospective seroepidemiologic study.

    PubMed

    Argüello, D Fermín; Tomashek, Kay M; Quiñones, Luz; Beltran, Manuela; Acosta, Luz; Santiago, Luis M; Biggerstaff, Brad J; Garcia-Rivera, Enid J; Sun, Wellington; Pollissard-Gadroy, Laurence; Luxemburger, Christine; Hunsperger, Elizabeth

    2015-03-01

    Dengue is a potentially fatal acute febrile illness caused by the mosquito-borne dengue viruses (DENV-1 to -4). To estimate DENV seroincidence in school-aged children, a 1-year prospective cohort study was conducted in Patillas, Puerto Rico; 10- to 18-year-olds (N = 345) were randomly selected from 13 public schools. At enrollment, 49.8% of the entire cohort had DENV immunoglobulin G (IgG) anti-DENV antibodies, and there were individuals with neutralizing antibodies specific to each of the four DENV. The mean age of participants with incident DENV infection was 13.4 years. The 1-year seroincidence rate was 5.6%, and 61.1% of infections were inapparent. Having IgG anti-DENV at enrollment was associated with seroincidence (risk ratio = 6.8). Acute febrile illnesses during the study period were captured by a fever diary and an enhanced and passive surveillance system in the municipios of Patillas and Guayama. In summary, at enrollment, nearly one-half of the participants had a prior DENV infection, with the highest incidence in the 10- to 11-year-olds, of which most were inapparent infections, and symptomatic infections were considered mild.

  1. Evaluation of RT-PCR as a tool for diagnosis of secondary dengue virus infection.

    PubMed

    Sa-ngasang, Areerat; Wibulwattanakij, Sasitorn; Chanama, Sumalee; O-rapinpatipat, Anantchai; A-nuegoonpipat, Atchareeya; Anantapreecha, Surapee; Sawanpanyalert, Pathom; Kurane, Ichiro

    2003-01-01

    Dengue fever and dengue hemorrhagic fever are serious illnesses in many tropical and subtropical countries. Laboratory tests are essential for the confirmation of dengue virus infection. In the present study, we examined the reliability of reverse transcriptase polymerase chain reaction (RT-PCR) in the laboratory diagnosis of dengue, especially in secondary dengue virus infections. We defined the day when fever subsided as fever day 0. In primary dengue virus infection, the dengue viral genome was detected in all of the 7 samples which were collected on fever day -1 or earlier, in 3 of 4 samples on fever day 0, and in 1 of 2 samples on fever day 1. None of the samples collected on fever day 2 or later were positive by RT-PCR. In secondary dengue virus infection, the dengue viral genome was detected in all of the 28 samples which were collected on fever day -2 or earlier, in 25 of 26 on fever day -1, in 29 of 34 on fever day 0, and in 5 of 10 on fever days 1-2. None of the samples collected on fever day 3 or later were positive. Virus isolation and direct titration were attempted using the plasma samples. When the data of secondary infection cases were analyzed based on fever day, dengue viruses were isolated from all of the 5 samples which were collected on fever day -2 or earlier, in 5 of 13 samples on fever day -1, and in 4 of 22 on fever day 0, but were not isolated from any of the 4 samples collected on fever days 1-2. Viruses were directly detected in 7 of 11 samples on fever day -2 or earlier, in 4 of 13 on fever day -1, and in 1 of 16 on fever day 0. These results indicate that RT-PCR is more sensitive than virus isolation and direct virus titration for determining secondary dengue virus infection. The results also suggest that RT-PCR is a useful diagnostic test for confirmation of dengue virus infection in secondary infection as well as in primary infection, especially when plasma samples are collected before the fever subsides.

  2. Clinical observations on virologically confirmed fatal dengue infections in Jakarta, Indonesia.

    PubMed

    Sumarmo; Wulur, H; Jahja, E; Gubler, D J; Suharyono, W; Sorensen, K

    1983-01-01

    Thirty virologically confirmed cases of dengue infection with a fatal outcome were studied clinically in Jakarta, Indonesia, from 1975 to 1978. All 4 dengue virus serotypes were isolated from fatal cases, but dengue type 3 was responsible for 21 (70%) of these isolates, compared to only 47% of isolates from all cases of dengue infection. The majority (60%) of these 30 cases were males in the 5-9-year age group. Nonspecific signs and symptoms in the fatal cases were no different from those in patients who survived dengue infection, but 70% of the patients with fatal outcome had one or more signs of encephalitis, primarily convulsions and somnolence; 3 of them developed spastic tetraparesis before death and 2 died of an illness clinically compatible with viral encephalitis. Other unexpected observations were that only 63% of the patients had classical dengue shock syndrome with haemoconcentration, thrombocytopenia and shock. A high percentage (80%) had gastrointestinal haemorrhage, and in 9 patients (30%) this was severe enough to cause shock and death. In these 9 cases, the gastrointestinal haemorrhage and haematemesis began before the onset of shock and there was no evidence of haemoconcentration or pleural effusion at any time during hospitalization. According to certain widely accepted criteria, these patients would not be diagnosed as dengue haemorrhagic fever (DHF). But as they made up nearly one-third of the confirmed fatal dengue infections in this study and had massive gastrointestinal haemorrhages with thrombocytopenia, the definition of DHF should be changed to include this type of patient. It is proposed that the disease should be more realistically classified as dengue fever with or without haemorrhage and dengue shock syndrome.

  3. 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. PMID:26603900

  4. 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.

  5. The ubiquitin-proteasome pathway is important for dengue virus infection in primary human endothelial cells.

    PubMed

    Kanlaya, Rattiyaporn; Pattanakitsakul, Sa-nga; Sinchaikul, Supachok; Chen, Shui-Tein; Thongboonkerd, Visith

    2010-10-01

    Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the most severe forms of dengue virus infection with hemorrhage and plasma leakage. However, pathogenic mechanisms of DHF and DSS remain poorly understood. We therefore investigated host responses as determined by changes in the cellular proteome of primary human endothelial cells upon infection with dengue virus serotype 2 (DEN-2) at a multiplicity of infection (MOI) of 10 for 24 h. Two-dimensional PAGE and quantitative intensity analysis revealed 38 significantly altered protein spots (16 upregulated and 22 downregulated) in DEN-2-infected cells compared to mock controls. These altered proteins were successfully identified by mass spectrometry, including those involved in oxidative stress response, transcription and translation, cytoskeleton assembly, protein degradation, cell growth regulation, apoptosis, cellular metabolism, and antiviral response. The proteomic data were validated by Western blot analyses [upregulated ubiquitin-activating enzyme E1 (UBE1) and downregulated annexin A2] and an immunofluorescence study (upregulated MxA). Interestingly, we found that MxA was colocalized with DEN-2 viral capsid protein, strengthening its role as an antiviral protein. Moreover, we also identified upregulation of a proteasome subunit. Our functional study revealed the significant role of ubiquitination in dengue infection and UBE1 inhibition by its specific inhibitor (UBEI-41) caused a significant reduction in the level of viral protein synthesis and its infectivity. Our findings suggest that various biological processes were triggered in response to dengue infection, particularly antiviral IFN and ubiquitin-proteasome pathways.

  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. 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

  8. A portable approach for the surveillance of dengue virus-infected mosquitoes.

    PubMed

    Muller, David A; Frentiu, Francesca D; Rojas, Alejandra; Moreira, Luciano A; O'Neill, Scott L; Young, Paul R

    2012-07-01

    Dengue virus is the most significant human viral pathogen spread by the bite of an infected mosquito. With no vaccine or antiviral therapy currently available, disease prevention relies largely on surveillance and mosquito control. Preventing the onset of dengue outbreaks and effective vector management would be considerably enhanced through surveillance of dengue virus prevalence in natural mosquito populations. However, current approaches to the identification of virus in field-caught mosquitoes require relatively slow and labor intensive techniques such as virus isolation or RT-PCR involving specialized facilities and personnel. A rapid and portable method for detecting dengue virus-infected mosquitoes is described. Using a hand held battery operated homogenizer and a dengue diagnostic rapid strip the viral protein NS1 was detected as a marker of dengue virus infection. This method could be performed in less than 30 min in the field, requiring no downstream processing, and is able to detect a single infected mosquito in a pool of at least 50 uninfected mosquitoes. The method described in this study allows rapid, real-time monitoring of dengue virus presence in mosquito populations and could be a useful addition to effective monitoring and vector control responses. PMID:22575689

  9. Differential clinical outcome of dengue infection among patients with and without HIV infection: a matched case-control study.

    PubMed

    Pang, Junxiong; Thein, Tun-Linn; Lye, David C; Leo, Yee-Sin

    2015-06-01

    Clinical characteristics and outcome among dengue patients with and without human immunodeficiency virus (HIV) infection remain elusive. A total of 10 dengue virus (DENV)-HIV Chinese patients were compared with 40 Chinese dengue patients without HIV, who were matched for age, gender, type of care received, methods, and year of dengue diagnosis from 2005 to 2008. Univariate and multivariate conditional logistics regression were applied. DENV-HIV patients were significantly associated with the World Health Organization (WHO) 2009 severe dengue (conditional odds ratio [COR] = 5.72; 95% confidence interval [CI] = 1.01-32.64) but not with the WHO 1997 dengue hemorrhagic fever/dengue shock syndrome (COR = 0.40; 95% CI = 0.09-1.71). This is mainly due to severe plasma leakage and the lack of hemorrhagic manifestations. Hospitalization duration was longer for DENV-HIV patients (10.5 days; interquartile range [IQR] = 5.5-26.3 days) compared with dengue patients (5 days; IQR = 4-6 days). There were no significant differences in presentation of clinical warning signs and symptoms at admission and during hospitalization, except for rash (adjusted COR [ACOR] = 0.06; 95% CI = 0.03-0.92). DENV-HIV patients were associated with higher pulse rate (ACOR = 1.13; 95% CI = 1.02-1.25), eosinophils proportion (ACOR = 3.07; 95% CI = 1.12-8.41) and lower hematocrit level (ACOR = 0.79; 95% CI = 0.64-0.98) compared with dengue patients. Even though DENV-HIV patients may present similarly to dengue patients, they may be more likely to have severe dengue outcome. Hence, close monitoring of DENV-HIV patients is highly recommended as part of dengue clinical care and management.

  10. Antibody to dengue 1 detected more than 60 years after infection.

    PubMed

    Imrie, Allison; Meeks, Janet; Gurary, Alexandra; Sukhbaatar, Munkhzul; Truong, Thang Thua; Cropp, C Bruce; Effler, Paul

    2007-12-01

    We investigated the duration of humoral responses to dengue virus infection in individuals who recalled experiencing dengue fever-like illnesses at the time of the Second World War, when dengue fever epidemics occurred throughout the Pacific and Southeast Asia. In July 1943 dengue fever reappeared in Hawaii following an interval of 31 years. Over the next 12 months a total of 1498 locally transmitted cases were reported, and at least 46 imported cases were identified, most of which were among members of the military returning from the Pacific Theatre of the war. Serum samples collected in 2005, more than 60 years after onset of symptoms, were tested for the presence of dengue-specific antibodies using a rapid ELISA test, and by plaque reduction neutralization test. Four of seven samples were positive for dengue-specific IgG and demonstrated neutralization titers >or=160 to dengue 1. We describe the existence of dengue-specific antibodies in the serum of people infected more than 60 years earlier.

  11. Preexisting neutralizing antibody responses distinguish clinically inapparent and apparent dengue virus infections in a Sri Lankan pediatric cohort.

    PubMed

    Corbett, Kizzmekia S; Katzelnick, Leah; Tissera, Hasitha; Amerasinghe, Ananda; de Silva, Aruna Dharshan; de Silva, Aravinda M

    2015-02-15

    Dengue viruses (DENVs) are mosquito-borne flaviviruses that infect humans. The clinical presentation of DENV infection ranges from inapparent infection to dengue hemorrhagic fever and dengue shock syndrome. We analyzed samples from a pediatric dengue cohort study in Sri Lanka to explore whether antibody responses differentiated clinically apparent infections from clinically inapparent infections. In DENV-naive individuals exposed to primary DENV infections, we observed no difference in the quantity or quality of acquired antibodies between inapparent and apparent infections. Children who experienced primary infections had broad, serotype-cross-neutralizing antibody responses that narrowed in breadth to a single serotype over a 12-month period after infection. In DENV immune children who were experiencing a repeat infection, we observed a strong association between preexisting neutralizing antibodies and clinical outcome. Notably, children with preexisting monospecific neutralizing antibody responses were more likely to develop fever than children with cross-neutralizing responses. Preexisting DENV neutralizing antibodies are correlated with protection from dengue disease.

  12. Clinical and upper gastroendoscopic features of patients with dengue virus infection.

    PubMed

    Wang, J Y; Tseng, C C; Lee, C S; Cheng, K P

    1990-01-01

    Clinical observation was made on 238 dengue fever cases during an epidemic in Taiwan from September to November 1988. Dengue virus infection type 1 was responsible for all cases. The majority of patients had acute onset of fever with abdominal pain, diarrhoea, and vomiting. Gastrointestinal haemorrhage with manifestation of haematemesis and/or melena was observed in 28 (11.8%) of our patients. The clinical gastrointestinal features in patients with a peptic ulcer history were not different from those in patients without it. There was no significant difference in incidence of gastrointestinal manifestations between premedication and non-premedication patients. Sixty-six non-premedication patients in our series were examined by gastroduodenoscopy. Haemorrhagic gastritis was the most common finding in 27 (40.9%) patients. The incidence of gastric and/or duodenal ulcerations was higher in patients with a peptic ulcer history compared with those without it (P less than 0.01). However, the incidence of upper gastrointestinal bleeding was similar between these two groups (19.2% vs 9.8%). Thrombocytopenia in patients with gastrointestinal haemorrhage was more prominent than in those without it (P less than 0.005). This implied that thrombocytopenia might be one of the predisposing factors for gastrointestinal haemorrhage.

  13. 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. PMID:27560782

  14. 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

  15. Dengue: a new challenge for neurology

    PubMed Central

    Puccioni-Sohler, Marzia; Orsini, Marco; Soares, Cristiane N.

    2012-01-01

    Dengue infection is a leading cause of illness and death in tropical and subtropical regions of the world. Forty percent of the world's population currently lives in these areas. The clinical picture resulting from dengue infection can range from relatively minor to catastrophic hemorrhagic fever. Recently, reports have increased of neurological manifestations. Neuropathogenesis seems to be related to direct nervous system viral invasion, autoimmune reaction, metabolic and hemorrhagic disturbance. Neurological manifestations include encephalitis, encephalopathy, meningitis, Guillain-Barré syndrome, myelitis, acute disseminated encephalomyelitis, polyneuropathy, mononeuropathy, and cerebromeningeal hemorrhage. The development of neurological symptoms in patients with positive Immunoglobulin M (IgM) dengue serology suggests a means of diagnosing the neurological complications associated with dengue. Viral antigens, specific IgM antibodies, and the intrathecal synthesis of dengue antibodies have been successfully detected in cerebrospinal fluid. However, despite diagnostic advancements, the treatment of neurological dengue is problematic. The launch of a dengue vaccine is expected to be beneficial. PMID:23355928

  16. Estimates of dengue force of infection in children in Colombo, Sri Lanka.

    PubMed

    Tam, Clarence C; Tissera, Hasitha; de Silva, Aravinda M; De Silva, Aruna Dharshan; Margolis, Harold S; Amarasinge, Ananda

    2013-01-01

    Dengue is the most important vector-borne viral disease worldwide and a major cause of childhood fever burden in Sri Lanka, which has experienced a number of large epidemics in the past decade. Despite this, data on the burden and transmission of dengue virus in the Indian Subcontinent are lacking. As part of a longitudinal fever surveillance study, we conducted a dengue seroprevalence survey among children aged <12 years in Colombo, Sri Lanka. We used a catalytic model to estimate the risk of primary infection among seronegative children. Over 50% of children had IgG antibodies to dengue virus and seroprevalence increased with age. The risk of primary infection was 14.1% per year (95% CI: 12.7%-15.6%), indicating that among initially seronegative children, approximately 1 in 7 experience their first infection within 12 months. There was weak evidence to suggest that the force of primary infection could be lower for children aged 6 years and above. We estimate that there are approximately 30 primary dengue infections among children <12 years in the community for every case notified to national surveillance, although this ratio is closer to 100:1 among infants. Dengue represents a considerable infection burden among children in urban Sri Lanka, with levels of transmission comparable to those in the more established epidemics of Southeast Asia.

  17. Mathematical model for Dengue with three states of infection

    NASA Astrophysics Data System (ADS)

    Hincapie, Doracelly; Ospina, Juan

    2012-06-01

    A mathematical model for dengue with three states of infection is proposed and analyzed. The model consists in a system of differential equations. The three states of infection are respectively asymptomatic, partially asymptomatic and fully asymptomatic. The model is analyzed using computer algebra software, specifically Maple, and the corresponding basic reproductive number and the epidemic threshold are computed. The resulting basic reproductive number is an algebraic synthesis of all epidemic parameters and it makes clear the possible control measures. The microscopic structure of the epidemic parameters is established using the quantum theory of the interactions between the atoms and radiation. In such approximation, the human individual is represented by an atom and the mosquitoes are represented by radiation. The force of infection from the mosquitoes to the humans is considered as the transition probability from the fundamental state of atom to excited states. The combination of computer algebra software and quantum theory provides a very complete formula for the basic reproductive number and the possible control measures tending to stop the propagation of the disease. It is claimed that such result may be important in military medicine and the proposed method can be applied to other vector-borne diseases.

  18. Proteomic analysis of host responses in HepG2 cells during dengue virus infection.

    PubMed

    Pattanakitsakul, Sa-Nga; Rungrojcharoenkit, Kamonthip; Kanlaya, Rattiyaporn; Sinchaikul, Supachok; Noisakran, Sansanee; Chen, Shui-Tein; Malasit, Prida; Thongboonkerd, Visith

    2007-12-01

    Dengue virus infection remains a public health problem worldwide. However, its pathogenic mechanisms and pathophysiology are still poorly understood. We performed proteomic analysis to evaluate early host responses (as indicated by altered proteins) in human target cells during dengue virus infection. HepG2 cells were infected with dengue virus serotype 2 (DEN-2) at multiplicity of infection (MOI) of 0.1, 0.5, and 1.0. Quantitative analyses of DEN-2 infection and cell death at 12, 24, and 48 h postinfection showed that the MOI of 1.0 with 24 h postinfection duration was the optimal condition to evaluate early host responses, as this condition provided the high %Infection ( approximately 80%), while %Cell death ( approximately 20%) was comparable to that of the mock-control cells. Proteins derived from the mock-control and DEN-2-infected cells were resolved by 2-D PAGE ( n = 5 gels for each group) and visualized by SYPRO Ruby stain. Quantitative intensity analysis revealed 17 differentially expressed proteins, which were successfully identified by peptide mass fingerprinting. Most of these altered proteins were the key factors involved in transcription and translation processes. Further functional study on these altered proteins may lead to better understanding of the pathogenic mechanisms and host responses to dengue virus infection, and also to the identification of new therapeutic targets for dengue virus infection.

  19. 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

  20. Dengue type 3 virus infections in European travellers returning from the Comoros and Zanzibar, February-April 2010.

    PubMed

    Gautret, P; Simon, F; Hervius Askling, H; Bouchaud, O; Leparc-Goffart, I; Ninove, L; Parola, P

    2010-04-15

    In late February-early April 2010, five cases of dengue fever were diagnosed in returning travellers in Europe in EurotravNet sites in Sweden and France in patients with travel history to the Comoros and/or Zanzibar, Tanzania. Four cases were non-complicated dengue fever and one case dengue hemorrhagic fever. Three patients were viraemic at the time of diagnosis and infected with Dengue type 3 virus.

  1. The Potential Impact of Vaccination on the Dynamics of Dengue Infections.

    PubMed

    Knipl, Diána; Moghadas, Seyed M

    2015-12-01

    Dengue, classified as a 'neglected topical disease', is currently regarded globally as the most important mosquito-borne viral disease, which inflicts substantial socioeconomic and health burden in many tropical and subtropical regions of the world. While efforts continue towards developing and improving the efficacy of a tetravalent vaccine to protect individuals against all dengue virus serotypes, the long-term epidemiological impact of vaccination remains elusive. We develop a serotype-specific, vector-host compartmental model to evaluate the effect of vaccination in the presence of antibody-dependent enhancement and cross-protection following recovery from primary infection. Reproducing the reported multi-annual patterns of dengue infection, our model projects that vaccination can dramatically reduce the overall incidence of the disease. However, if the duration of vaccine-induced protection is shorter than the average lifetime of the human population, vaccination can potentially increase the incidence of severe infection of dengue haemorrhagic fever due to the effects of antibody-dependent enhancement. The magnitude and timelines for this increase depend strongly on the efficacy and duration of the vaccine-induced protection. Corresponding to the current estimates of vaccine efficacy, we show that dengue eradication is infeasible using an imperfect vaccine. Furthermore, for a vaccine that induces lifetime protection, a nearly full coverage of infant vaccination is required for dengue elimination. Our findings suggest that other vector control measures may still play a significant role in dengue prevention even when a vaccine with high protection efficacy becomes available. PMID:26585748

  2. 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

  3. Plasma concentrations of sVCAM-1 and severity of dengue infections.

    PubMed

    Murgue, B; Cassar, O; Deparis, X

    2001-09-01

    Adhesion molecules are essential for the immune response. They are involved in the regulation of cell-to-cell contact, thereby enabling leukocytes to communicate. Circulating forms of adhesion molecules are found in the serum of healthy individuals. Raised levels have been associated with disease severity in HCV and other infections and thus appear to be good markers of endothelial damage. The levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and of sP and sL-selectin in the plasma of children hospitalised for dengue in French Polynesia were monitored. Studies from the 1996/1997 dengue-2 outbreak, showed that levels of sVCAM-1 increase steadily during the febrile period, peak on day 7, and then decline relatively rapidly. Disregarding the time frame within the febrile period, sVCAM-1 levels were always higher compared to controls. There was a significant association between sVCAM-1 levels and dengue haemorrhagic fever, a severe manifestation of dengue virus infection characterised by plasma leakage. No association was apparent between sVCAM-1 levels and primary vs. secondary dengue virus infections. Levels of sP-selectin and sL-selectin were significantly higher in primary compared with secondary infection but were not different in patients presenting with plasma leakage. Lastly, sVCAM-1 levels were significantly higher in an outbreak of severe disease in 1989/1990 (dengue-3) when compared to a non-severe outbreak in 1988/1989 (dengue-1) and a mild outbreak in 1996/1997 (dengue-2). The results suggested that levels of sVCAM-1 production might prove to be a useful marker in the management of severe dengue.

  4. 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. PMID:27427141

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

    PubMed

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

    2016-03-01

    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.

  6. Dengue antibody prevalence in German travelers.

    PubMed

    Wichmann, Ole; Lauschke, Annekathrin; Frank, Christina; Shu, Pei-Yun; Niedrig, Matthias; Huang, Jyh-Hsiung; Stark, Klaus; Jelinek, Tomas

    2005-05-01

    We studied 2,259 German citizens after they returned from dengue-endemic countries from 1996 to 2004. Serotype-specific dengue antibodies indicated acute infections in 51 (4.7%) travelers with recent fever and 13 (1.1%) travelers with no recent fever, depending largely on destination and epidemic activity in the countries visited.

  7. Airport sentinel surveillance and entry quarantine for dengue infections following a fever screening program in Taiwan

    PubMed Central

    2012-01-01

    Background Dengue has not reached an endemic status in Taiwan; nevertheless, we have implemented a fever screening program at airports for the early detection of febrile passengers with a dengue infection. This study is intended to assess the performance of the airport screening procedures for dengue infection. Methods We analyzed data from the national surveillance system of the Taiwan Centers for Disease Control. We included the imported dengue cases reported by sentinel airports and clinics as well as the domestic cases from 2007–2010. Results Approximately 44.9% (95%CI: 35.73-54.13%) of the confirmed imported dengue cases with an apparent symptom (febrile) in the viremic stage were detected via the airport fever screening program, with an estimated positive predictive value of 2.36% (95% CI: 0.96- 3.75%) and a negative predictive value > 99.99%. Fluctuations in the number of the symptomatic imported dengue cases identified in the airports (X) were associated with the total number of imported dengue cases (Y) based on a regression analysis of a biweekly surveillance (i.e., n = 104, R2X:Y = 0.61, P < 0.005). Additionally, the fluctuating patterns in the cumulative numbers of the imported dengue cases (X) with a 1–2 month lead time (t) was in parallel with that of the domestic dengue cases (Y) based on a consecutive 4-year surveillance (i.e., n = 48, R2X(t-1):Y = 0.22, R2X(t-2):Y = 0.31, P < 0.001) from 2007–2010. Conclusions A moderate sensitivity of detecting dengue at the airports examined in this study indicated some limitations of the fever screening program for the prevention of importation. The screening program could assist in the rapid triage for self-quarantine of some symptomatic dengue cases that were in the viremic stage at the borders and contribute to active sentinel surveillance; however, the blocking of viral transmission to susceptible populations (neighbors or family) from all of the viremic travelers

  8. Dengue hemorrhagic Fever caused by sequential dengue 1-3 virus infections over a long time interval: Havana epidemic, 2001-2002.

    PubMed

    Alvarez, Mayling; Rodriguez-Roche, Rosmari; Bernardo, Lídice; Vázquez, Susana; Morier, Luis; Gonzalez, Daniel; Castro, Osvaldo; Kouri, Gustavo; Halstead, Scott B; Guzman, Maria G

    2006-12-01

    A dengue epidemic caused by dengue virus 3 (DENV-3) occurred in Cuba in 2001-2002. It included cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). We report neutralizing antibody studies on sera from 54 of 78 DHF/DSS patients that provide evidence of infections occurring in the sequence DENV-1 followed by DENV-3. No sera showed infection in the sequence DENV-2 followed by DENV-3. Some sera showed a pattern of infection in the sequence DENV-1 followed by DENV-2 and then DENV-3. However definitive categorization of a tertiary infection was not possible because of broadly reactive antibodies, which could have been raised by infections in the sequence DENV-1 then DENV-3.

  9. Symptomatic versus inapparent outcome in repeat dengue virus infections is influenced by the time interval between infections and study year.

    PubMed

    Montoya, Magelda; Gresh, Lionel; Mercado, Juan Carlos; Williams, Katherine L; Vargas, Maria José; Gutierrez, Gamaliel; Kuan, Guillermina; Gordon, Aubree; Balmaseda, Angel; Harris, Eva

    2013-01-01

    Four dengue virus serotypes (DENV1-4) circulate globally, causing more human illness than any other arthropod-borne virus. Dengue can present as a range of clinical manifestations from undifferentiated fever to Dengue Fever to severe, life-threatening syndromes. However, most DENV infections are inapparent. Yet, little is known about determinants of inapparent versus symptomatic DENV infection outcome. Here, we analyzed over 2,000 DENV infections from 2004 to 2011 in a prospective pediatric cohort study in Managua, Nicaragua. Symptomatic cases were captured at the study health center, and paired healthy annual samples were examined on a yearly basis using serological methods to identify inapparent DENV infections. Overall, inapparent and symptomatic DENV infections were equally distributed by sex. The mean age of infection was 1.2 years higher for symptomatic DENV infections as compared to inapparent infections. Although inapparent versus symptomatic outcome did not differ by infection number (first, second or third/post-second DENV infections), substantial variation in the proportion of symptomatic DENV infections among all DENV infections was observed across study years. In participants with repeat DENV infections, the time interval between a first inapparent DENV infection and a second inapparent infection was significantly shorter than the interval between a first inapparent and a second symptomatic infection. This difference was not observed in subsequent infections. This result was confirmed using two different serological techniques that measure total anti-DENV antibodies and serotype-specific neutralizing antibodies, respectively. Taken together, these findings show that, in this study, age, study year and time interval between consecutive DENV infections influence inapparent versus symptomatic infection outcome, while sex and infection number had no significant effect. Moreover, these results suggest that the window of cross-protection induced by a first

  10. 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. PMID:27140859

  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. Dengue virus infection during post-epidemic period in Delhi, India.

    PubMed

    Vajpayee, M; Mohankumar, K; Wali, J P; Dar, L; Seth, P; Broor, S

    1999-09-01

    Dengue fever (DF) and dengue hemorrhagic fever (DHF) are major public health problems in India. During the period following an epidemic, a study was carried out using virological and serological tests for confirmation of suspected cases of dengue virus infection in fever cases presenting to the All India Institute of Medical Sciences. Serum samples of suspected DF/DHF cases were processed from January to December 1997. In 37 samples from patients with fever of less than 5-day duration, received on ice, virus isolation was attempted in C6/36 clone of Aedes albopictus cell line, followed by indirect fluorescent antibody staining with monoclonal antibodies to dengue viruses 1 to 4. One hundred and forty-three serum samples from patients with more than 5 days fever were tested for dengue specific IgM antibody by either MAC-ELISA or a rapid immunochromatographic assay. Dengue virus type 1 was demonstrated by culture in 8 (21.6%) of 37 serum samples and IgM antibody could be detected in 42 (29.4%) of the 143 serum samples by the serological methods. The peak of dengue virus infection was seen from September to November 1997.

  13. Dual infection with dengue virus 3 and human immunodeficiency virus 1 in Havana, Cuba.

    PubMed

    Gonzalez, Daniel; Limonta, Daniel; Bandera, Juan Francisco; Perez, Jorge; Kouri, Gustavo; Guzman, Maria G

    2009-01-01

    Although dengue virus (DEN) endemic regions overlap with human immunodeficiency virus 1 (HIV) high incidence areas, little has been documented on HIV and DEN mixed infection. Here we report DEN/HIV concurrent infections recorded during the DEN-3 epidemic in 2001-2002 in Havana. Serologic-confirmed DEN is described in two HIV-infected subjects with dengue fever symptoms. Although patients had dengue disease, the CD4+ cells remained within normal levels and no accelerated progression of HIV disease was observed. To our knowledge, DEN cases caused by DEN-3 in HIV-infected individuals have not been reported previously. Further research is needed to diagnose this likely underreported mixed viral infection in DEN endemic areas.

  14. Travel-related Dengue Virus Infection, the Netherlands, 2006–2007

    PubMed Central

    Sonder, Gerard J.B.; Zaaijer, Hans L.; van Gool, Tom; Kint, Joan A.P.C.M.; van den Hoek, Anneke

    2011-01-01

    To assess the incidence of and risk factors for clinical and subclinical dengue virus (DENV) infection, we prospectively studied 1,207 adult short-term travelers from the Netherlands to dengue-endemic areas. Participants donated blood samples for serologic testing before and after travel. Blood samples were tested for antibodies against DENV. Seroconversion occurred in 14 (1.2%) travelers at risk. The incidence rate was 14.6 per 1,000 person-months. The incidence rate was significantly higher for travel during the rainy months. Dengue-like illness occurred in 5 of the 14 travelers who seroconverted. Seroconversion was significantly related to fever, retro-orbital pain, myalgia, arthralgia, and skin rash. The risk for DENV infection for short-term travelers to dengue-endemic areas is substantial. The incidence rate for this study is comparable with that in 2 other serology-based prospective studies conducted in the 1990s. PMID:21529390

  15. Travel-related dengue virus infection, The Netherlands, 2006-2007.

    PubMed

    Baaten, Gijs G G; Sonder, Gerard J B; Zaaijer, Hans L; van Gool, Tom; Kint, Joan A P C M; van den Hoek, Anneke

    2011-05-01

    To assess the incidence of and risk factors for clinical and subclinical dengue virus (DENV) infection, we prospectively studied 1,207 adult short-term travelers from the Netherlands to dengue-endemic areas. Participants donated blood samples for serologic testing before and after travel. Blood samples were tested for antibodies against DENV. Seroconversion occurred in 14 (1.2%) travelers at risk. The incidence rate was 14.6 per 1,000 person-months. The incidence rate was significantly higher for travel during the rainy months. Dengue-like illness occurred in 5 of the 14 travelers who seroconverted. Seroconversion was significantly related to fever, retro-orbital pain, myalgia, arthralgia, and skin rash. The risk for DENV infection for short-term travelers to dengue-endemic areas is substantial. The incidence rate for this study is comparable with that in 2 other serology-based prospective studies conducted in the 1990s.

  16. Secondary dengue infection in schoolchildren in a dengue endemic area in the state of Rio de Janeiro, Brazil.

    PubMed

    da Cunha, R V; Dias, M; Nogueira, R M; Chagas, N; Miagostovich, M P; Schatzmayr, H G

    1995-01-01

    A seroepidemiologic survey was carried out in schoolchildren from public schools of the Niterói municipality, state of Rio de Janeiro, Brazil, after a period of sequential epidemics by dengue virus type 1 and 2 (DEN-1 and DEN-2). 450 blood samples were obtained by fingertip puncture and collected on filter paper discs. The hemagglutination inhibition (HAI) test was carried out using DEN-1 and DEN-2 antigens. HAI titres were demonstrated in 66% (297/450) of the sera and the geometric means of the titres were 1/182 and 1/71 for DEN-1 and DEN-2, respectively. Secondary infections were observed in 61% (181/297) of positive cases. Among these, 75% (135/181) were under fifteen years old. No dengue haemorrhagic fever (DHF) was reported in these children. Asymptomatic or oligosymptomatic infections were detected in 56% of the studied population. The absolute and relative frequencies of positive tests by age group and sex did not evidence statistically significant difference. The number of individuals infected probably produced a immunologic barrier responsible for the non occurrence of dengue epidemic in the latter years.

  17. Infection of bone marrow cells by dengue virus in vivo.

    PubMed

    Noisakran, Sansanee; Onlamoon, Nattawat; Hsiao, Hui-Mien; Clark, Kristina B; Villinger, Francois; Ansari, Aftab A; Perng, Guey Chuen

    2012-03-01

    Abnormal bone marrow (BM) suppression is one of the hallmarks of dengue virus (DENV) infection in patients. Although the etiology remains unclear, direct viral targeting of the BM has been reasoned to be a contributing factor. The present studies were carried out in an effort to determine the potential effect of DENV infection on the cellularity of BM using a previously established nonhuman primate model of DENV-induced coagulopathy. BM aspirates were collected at various times from the infected nonhuman primate and cells were phenotypically defined and isolated using standard flow cytometry (fluorescence-activated cell sorting). These isolated cells were subjected to detection of DENV utilizing quantitative real-time reverse transcription polymerase chain reaction, electron microscopy, and immunostaining techniques. DENV RNA was detectable by quantitative real-time reverse transcription polymerase chain reaction in BM specimens and the presence of DENV-like particles within platelet was confirmed by electron microscopy. Enumeration of BM cells revealed a transient surge in cellularity at day 1, followed by a gradual decline from days 2 to 10 post infection. Detailed phenotypic studies showed similar kinetics in the frequencies of CD41(+)CD61(+) cells, regardless of CD34 and CD45 expression. The CD61(+) cells were not only the predominant cells that stained for DENV antigen but fluorescence-activated cell sorting-assisted isolation of CD61(+) cells from the BM were shown to contain infectious DENV by coculture with Vero cells. These data support the view that intravenous infection of nonhuman primate with DENV leads to direct infection of the BM, which is likely to be a contributing factor for transient cell suppression in the peripheral blood characteristic of acute DENV infection.

  18. 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

  19. Dengue viruses - an overview.

    PubMed

    Bäck, Anne Tuiskunen; Lundkvist, Ake

    2013-01-01

    Dengue viruses (DENVs) cause the most common arthropod-borne viral disease in man with 50-100 million infections per year. Because of the lack of a vaccine and antiviral drugs, the sole measure of control is limiting the Aedes mosquito vectors. DENV infection can be asymptomatic or a self-limited, acute febrile disease ranging in severity. The classical form of dengue fever (DF) is characterized by high fever, headache, stomach ache, rash, myalgia, and arthralgia. Severe dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS, which can be fatal, is characterized by systemic shock. Despite intensive research, the underlying mechanisms causing severe dengue is still not well understood partly due to the lack of appropriate animal models of infection and disease. However, even though it is clear that both viral and host factors play important roles in the course of infection, a fundamental knowledge gap still remains to be filled regarding host cell tropism, crucial host immune response mechanisms, and viral markers for virulence.

  20. Association of FcγRIIa Polymorphism with Clinical Outcome of Dengue Infection: First Insight from Pakistan.

    PubMed

    Mohsin, Saima Naz; Mahmood, Saqib; Amar, Ali; Ghafoor, Farkhanda; Raza, Syed Mohsin; Saleem, Mahjabeen

    2015-10-01

    Dengue illness has been a major health concern in Pakistan during the last decade. Dengue infection can result in a spectrum of clinically distinct outcomes, ranging from asymptomatic infection to potentially life-threatening forms of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). A single-nucleotide polymorphism in FcγRIIa (rs1801274) results in altered affinity of the receptor for different subclasses of immunoglobulin G, and is a key player in determining the susceptibility to or protection from severe clinical infection of dengue. In this study, we analyzed the allelic and genotypic distribution of rs1801274 in subjects of Pakistani origin with subclinical dengue infection (n = 40), dengue fever (DF) (n = 40), and DHF/DSS (n = 30). We found that HH homozygotes and heterozygotes were significantly more likely to develop clinical dengue (odds ratio [OR] = 3.21, 95% confidence interval [CI] = 1.29-7.97, P = 0.009), either DF (OR = 2.82, 95% CI = 1.00-7.97, P = 0.045) or DHF/DSS (OR = 3.90, 95% CI = 1.13-13.07, P = 0.024) than the asymptomatic dengue infection. Results of allelic distribution comparisons and logistic regression analysis also supported the same relationship. The results suggest complex nature of interacting factors in determining the course for severe dengue illness.

  1. 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

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

    PubMed

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

    2016-01-19

    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.

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

    PubMed

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

    2016-01-19

    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

  4. 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. PMID:25131378

  5. The seroprevalence and seroincidence of dengue virus infection in western Kenya.

    PubMed

    Blaylock, Jason M; Maranich, Ashley; Bauer, Kristen; Nyakoe, Nancy; Waitumbi, John; Martinez, Luis J; Lynch, Julia

    2011-09-01

    Epidemics of dengue fever have been documented throughout the African continent over the past several decades, however little is known about the prevalence or incidence of dengue virus infection in the absence of an outbreak. No studies have analyzed the prevalence of dengue infection in western Kenya to date. This study describes the seroincidence and seroprevalence of dengue infection in western Kenya. Banked sera obtained from 354 healthy, afebrile children ages 12-47 months from Kisumu District, Kenya, were analyzed for antibodies to dengue virus using an IgG indirect ELISA. We found a seroprevalence of 1.1% (4 of 354 samples) and incidence of 8.5 seroconversions per 1000 persons per year in this study population. This appears to be similar to that previously reported in coastal regions of the country outside of known epidemic periods. Since there has never been a reported dengue epidemic in western Kenya, continued investigation and evaluation in a patient population presenting with fever is necessary to further confirm this finding.

  6. 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.

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

    PubMed

    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

    2015-12-01

    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.

  8. 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.

  9. Dengue virus 3 clinical isolates show different patterns of virulence in experimental mice infection.

    PubMed

    Ferreira, Gustavo P; Figueiredo, Leandra B; Coelho, Luiz F L; S, Policarpo A; Cecilio, Alzira B; Ferreira, Paulo C P; Bonjardim, Cláudio A; Arantes, Rosa M E; Campos, Marco A; Kroon, Erna G

    2010-07-01

    Dengue virus (DENV) may cause symptomatic infection with mild, undifferentiated febrile illness called classical dengue fever (DF) or a more severe disease, potentially fatal, known as dengue hemorrhagic fever (DHF) or dengue shock syndrome. The pathogenesis of DHF is based on the virulence of the infecting DENV and depends on the infecting serotypes and genotypes; it is also based on the immunopathogenesis that is mediated by host immune responses, including dengue virus-cross-reactive antibodies that augment the severity of infections. Involvement of central nervous system (CNS) is extensively described. The present study describes the virulence of DENV-3 isolates in a mouse model by intracranial (i.c.) inoculation with genotypes I and III. Our data suggest that, in this experimental model, DENV-3 genotype I may have the propensity to cause neurological disease in mice, whereas the genotype III is associated with asymptomatic infection in mice. Additionally, the symptomatic mice show a decrease of white blood cell count, infectious DENV in the brains and alterations in levels of IFN-gamma, IL-6 and MCP-1. The results confirm the mouse model as a way to study the biology of DENV-3 isolates and to improve the knowledge about the neurovirulence of the different genotypes of DENV.

  10. An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation.

    PubMed

    Reis, Sônia Regina Nogueira Ignácio; Sampaio, André Luiz Franco; Henriques, Maria das Graças Muller; Gandini, Mariana; Azeredo, Elzinandes Leal; Kubelka, Claire Fernandes

    2007-12-01

    An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune etiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applied for dengue fever.

  11. Dengue: a newly emerging viral infection in Andaman and Nicobar Islands, India.

    PubMed

    Chaaithanya, I K; Bhattacharya, D; Muruganandam, N; Thamizhmani, R; Babu, B V Suresh; Sundaram, S G; Matta, M; Singh, S S; Vijayachari, P

    2012-10-01

    Prior to 2009 dengue fever had not been reported in the Andaman and Nicobar archipelago. In 2009, a few patients with dengue fever-like illness were reported, some of whom tested positive for dengue antibodies. In 2010, 516 suspected cases were reported, including some with dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS); 80 (15·5%) were positive for dengue antibodies. DENV RNA was detected in five patients and PCR-based typing showed that three of these belonged to serotype 1 and two to serotype 2. This was confirmed by sequence typing. Two clones of dengue virus, one belonging to serotype 1 and the other to serotype 2 appeared to be circulating in Andaman. Emergence of severe diseases such as DHF and DSS might be due to recent introduction of a more virulent strain or because of the enhancing effect of sub-neutralizing levels of antibodies developed due to prior infections. There is a need to revise the vector-borne disease surveillance system in the islands.

  12. High levels of sTNFR p75 and TNF alpha in dengue-infected patients.

    PubMed

    Hober, D; Delannoy, A S; Benyoucef, S; De Groote, D; Wattré, P

    1996-01-01

    Soluble forms of the two molecular species of the cell surface TNF receptors (sTNFR p55 and sTNFR p75) can reduce the activity of TNF alpha but they may also enhance its function by stabilizing the active TNF alpha oligomer. Considering the pathophysiological importance of sTNFR p75 for the regulation of the bioavailability of TNF alpha in the body, we determined the serum levels of sTNFR p75 and TNF alpha in 45 children and 28 adults with laboratory-confirmed dengue infection by using immunoassays. The serum samples were obtained from day 1 to day 15 after the onset of the disease during the 1989-1990 outbreak of dengue-3 in Tahiti, French Polynesia. The patients were clinically classified as having dengue hemorrhagic fever (DHF) and graded according to the criteria of the World Health Organization (WHO) into four grades from less severe (grade I) to severe (grade IV). The sera of both children and adult patients of all severity grades contained higher levels of sTNFR p75 than the sera of control subjects. Although high levels of TNF alpha were also detected in children and adults among grade I, II, III and IV patients, we found no correlation between sTNFR p75 and TNF alpha. We observed in adults a moderate elevation of sTNFR p75 and TNF alpha in sera compared with that observed in children. The raised levels of immunoreactive sTNFR p75 and TNF alpha in all clinical groups of dengue-infected patients strongly indicate activation of the TNF alpha system during dengue infection. The balance between sTNFR p75 and TNF alpha may be altered in dengue infection. Further investigations are needed to understand the role of sTNFR p75 and TNF alpha in the pathogenesis of DHF and to improve the management of dengue infection.

  13. Dengue hemorrhagic fever patients with acute abdomen: clinical experience of 14 cases.

    PubMed

    Khor, Boon-Siang; Liu, Jien-Wei; Lee, Ing-Kit; Yang, Kuender D

    2006-05-01

    Among 328 patients with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 14 (4 men and 10 women, median age 44 years) had acute abdomen. DHF/DSS was initially suspected in only 2 of these 14 patients. Presumptive diagnoses of acute cholecystitis (6 acalculus and 4 calculus cholecystitis) were made in 10 patients, non-specific peritonitis in three patients, and acute appendicitis in one patients. Cholecystectomy, percutaneous transhepatic gallbladder drainage, and appendectomy were performed in three patients. Transfused blood in the three patients who underwent invasive procedures and the 11 patients who received supportive treatment included packed red blood cells (24 versus 0 units; P = 0.048), fresh frozen plasma (84 versus 0 units; P = 0.048), and platelets (192 versus 180 units; P = 0.003). Patients who underwent invasive procedures also had prolonged time in the hospital (median = 11 versus 7 days; P = 0.015). To avoid unnecessary invasive procedure-related morbidity and mortality, this report underscores the importance of a careful differential diagnosis in patients with acute abdomen in a dengue-endemic setting.

  14. Proposal of a Clinical Decision Tree Algorithm Using Factors Associated with Severe Dengue Infection

    PubMed Central

    Hussin, Narwani; Cheah, Wee Kooi; Ng, Kee Sing; Muninathan, Prema

    2016-01-01

    Background WHO’s new classification in 2009: dengue with or without warning signs and severe dengue, has necessitated large numbers of admissions to hospitals of dengue patients which in turn has been imposing a huge economical and physical burden on many hospitals around the globe, particularly South East Asia and Malaysia where the disease has seen a rapid surge in numbers in recent years. Lack of a simple tool to differentiate mild from life threatening infection has led to unnecessary hospitalization of dengue patients. Methods We conducted a single-centre, retrospective study involving serologically confirmed dengue fever patients, admitted in a single ward, in Hospital Kuala Lumpur, Malaysia. Data was collected for 4 months from February to May 2014. Socio demography, co-morbidity, days of illness before admission, symptoms, warning signs, vital signs and laboratory result were all recorded. Descriptive statistics was tabulated and simple and multiple logistic regression analysis was done to determine significant risk factors associated with severe dengue. Results 657 patients with confirmed dengue were analysed, of which 59 (9.0%) had severe dengue. Overall, the commonest warning sign were vomiting (36.1%) and abdominal pain (32.1%). Previous co-morbid, vomiting, diarrhoea, pleural effusion, low systolic blood pressure, high haematocrit, low albumin and high urea were found as significant risk factors for severe dengue using simple logistic regression. However the significant risk factors for severe dengue with multiple logistic regressions were only vomiting, pleural effusion, and low systolic blood pressure. Using those 3 risk factors, we plotted an algorithm for predicting severe dengue. When compared to the classification of severe dengue based on the WHO criteria, the decision tree algorithm had a sensitivity of 0.81, specificity of 0.54, positive predictive value of 0.16 and negative predictive of 0.96. Conclusion The decision tree algorithm proposed

  15. 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...

  16. Dengue myocarditis in Singapore: two case reports.

    PubMed

    Marques, N; Gan, V C; Leo, Y-S

    2013-06-01

    The authors report two cases of complicated dengue viral infection with acute myocarditis involving young male adults, of which one was fatal. The first case presented with typical signs of myocardial disease: chest pain and diaphoresis with myocardial depression in the electrocardiograph. The second case deteriorated rapidly and demised within the first day of admission. Histology of the heart muscles showed multiple small foci of myocyte necrosis surrounded by lymphocytes, in keeping with viral myocarditis. Both cases fulfilled the World Health Organization (WHO) diagnosis of probable dengue: the first case had positive dengue serology, both IgM and IgG at day six of illness, and the second case was polymerase chain reaction (PCR) positive for dengue and identified as serotype 2. Despite the severe outcome, both cases did not completely fulfil the criteria for dengue haemorrhagic fever (DHF). Although severe cardiac impairment is not commonly reported in dengue infection, it can be life threatening.

  17. [Laboratory diagnosis of dengue virus infections in Aragua State, Venezuela: October 1997-December 1998].

    PubMed

    Camacho, Daría Elena; Alvarez, Maritza; Rodríguez-Henríquez, Francisco; de Quintana, Maritza; Soler, Maritza; Chiarello, Anna; Sierra, Gloria; Comach, Guillermo

    2003-06-01

    The efficacy of a proactive dengue surveillance system to predict epidemics depends on the laboratory diagnostic capacity for an early detection of virus circulation. This study shows the results of the dengue virologic and serologic surveillance accomplished in Aragua State (Venezuela) from October 1997 to December 1998. Five hundred and forty seven sera from suspected dengue patients were tested using the techniques of Virus Isolation and Immunofluorescence Serotyping (VIIS), Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), Anti-dengue IgM Capture Enzyme Immunoassay (MAC-ELISA) and Haemagglutination Inhibition test (HI). Of the tested sera, 97.4% resulted positive to at least one technique; of these, 60.4% were classified as confirmed cases (virologically positives) and 39.6% as probable cases (virologically negatives/serologically positives). Though the majority of positive cases occurred during the 1997 and 1998 epidemic periods, the gradual increase of the seropositive rates between both periods suggested the incoming 1998 outbreak. Den-1 (51.2%), Den-2 (37.9%) and Den-4 (10.6%) infected patients were detected as well as one dual infection of Den-2 and Den-4 (0.3%). Dengue hyperendemicity (co-circulation of Den-1, Den-2 and Den-4) in Aragua State was confirmed together with the detection of few cases (6.5%) of Dengue Hemorrhagic Fever/Dengue Shock Syndrome cases (HF/DSS); 38.1% of these cases occurred in patients with secondary infections. The high percentage (85.7%) of DHF/DSS cases infected by Den-2 virus supports the reported virulence of this serotype.

  18. 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.

  19. 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. PMID:26910599

  20. 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

    2014-01-01

    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

  1. 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

  2. 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

    2014-01-01

    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.

  3. Molecular diagnosis and epidemiology of dengue virus infection.

    PubMed

    Chow, V T

    1997-11-01

    Early diagnosis of dengue fever contributes towards appropriate management of the disease and its potentially severe complications. Better and more rapid molecular procedures are increasingly available for detecting dengue viral RNA, antibodies and antigens. Using consensus primers based on the conserved non-structural-3 gene, the reverse transcription-polymerase chain reaction (RT-PCR) technique can amplify all four dengue virus types as well as certain flaviviruses. Consensus primers used together with four type-specific downstream primers in single-step or semi-nested RT-PCR formats can discriminate the specific dengue virus type by virtue of the diagnostic size of the RT-PCR target fragment on agarose gel electrophoresis. Alternatively, RT-PCR products may be labelled with digoxigenin and allowed to hybridise with individual biotinylated type-specific PCR primers which act as capture probes immobilised on solid phase via streptavidin-coated tubes. With automated instrumentation for enzyme-linked immunosorbent assay (ELISA), the hybridised RT-PCR products can be quantitated spectrophotometrically via anti-digoxigenin antibodies conjugated with an enzyme which reacts with colourimetric substrate. While RT-PCR is highly sensitive, specific and successfully identifies the dengue virus type in clinical serum samples and adult Aedes mosquitoes, it generally yields positive results in viraemic sera collected within 2 to 5 days of pyrexia. Sera obtained after the period of viraemia are more likely to be positive by serological tests such as IgM capture ELISA or the commercial Dengue Blot kit. The RT-PCR primers can also be utilised for direct cycle dideoxy DNA sequencing to monitor the molecular epidemiology and evolution of geographically and temporally separated virus strains. To exemplify this, nucleotide and amino acid sequence data as well as phylogenetic trees of several strains of dengue 1 and 2 viruses from patients and field-caught Aedes mosquitoes are

  4. A Study on Spectrum of Hepatobiliary Dysfunctions and Pattern of Liver Involvement in Dengue Infection

    PubMed Central

    Chattaraj, Sayan; Hajra, Adrija; Mukhopadhyay, Sabyasachi; Ganesan, Vijayan

    2016-01-01

    Introduction The most common arthropod-borne viral (arboviral) disease in humans is dengue. It is transmitted by female Aedes mosquitoes. These mosquitoes are widely distributed in subtropical and tropical areas of the world. Study of dengue infection and its complications are rare from countries like India. Aim In this prospective observational cross-sectional study, we intended to assess the frequency and degree of hepatobiliary dysfunction in adult patients with dengue infection presenting to a tertiary-care medical facility. Materials and Methods The details of all patients with serologically proved dengue fever admitted to a tertiary care hospital in eastern India from July 2014 to June 2015 were prospectively reviewed. We collected data including routine blood count, Liver Function Test (LFT), Prothrombin Time (PT), Activated Partial Prothrombin Time (APTT), abdominal ultrasonography from 110 patients. Results The maximum number of cases were seen in the age group between 46 years and 61 years and of all cases 55.5% were male and 44.5% were female. Pain abdomen and vomiting were the commonest presenting complaints next to fever which was present in all the cases. Elevated liver enzymes, abnormal values of PT and APTT, thrombocytopenia were observed more commonly in Dengue Shock Syndrome (DSS). Gall bladder wall thickening, thrombocytopenia were seen more commonly in both DSS and Dengue Haemorrhagic Fever (DHF). Plasma leakage such as ascites and pleural effusion on USG were seen more frequently in patients with DHF (76.9% and 73.1%) followed by DSS (72% and 68%) and DF (33.9% and 32.2%). Conclusion Hepatobiliary derangement is seen more commonly in severe case of dengue infection. Early recognition of these parameters can also be used as a predictor for assessing the disease severity. PMID:27437266

  5. A retrospective survey of dengue virus infection in fatal cases from an epidemic in Brazil.

    PubMed

    de Araújo, Josélio M Galvão; Schatzmayr, Hermann Gonçalves; de Filippis, Ana Maria Bispo; Dos Santos, Flávia Barreto; Cardoso, Maria Angélica; Britto, Constança; Coelho, Janice M C Oliveira; Nogueira, Rita Maria Ribeiro

    2009-01-01

    Dengue virus can infect many cell types from the vascular, muscular and hematological systems causing diverse clinical and pathological signs. The purpose of the present study was to investigate by different diagnostic methods dengue virus in human tissue specimens obtained from fatal cases (n=29) during a large-scale dengue fever epidemic in 2002 in the State of Rio de Janeiro, Brazil. The combination of four procedures provided diagnostic confirmation of DENV-3 infection in 26 (89.6%) out of the 29 suspected fatal cases. Dengue virus (DENV) was isolated from 2/74 (2.7%) tissue samples, inoculated into C6/36 cells and identified as DENV-3, nested RT-PCR accusing 22/72 (30.5%) samples as DENV-3. Real-time RT-PCR yielded the highest positivity rate, detecting viral RNA in 45/77 (58.4%) clinical specimens, including the liver (n=18), lung (n=8), spleen (n=8), brain (n=6), kidney (n=3), bone marrow (n=1) and heart (n=1). Immunohistochemical tests recognized the DENV antigen in 26/59 (44%) specimens. Given the accuracy and effectiveness of real-time RT-PCR in this investigation, this approach may play an important role for rapid diagnosis of dengue infections.

  6. Ileal perforation associated with dengue in the paediatric age group: an uncommon presentation.

    PubMed

    Kumar, Piyush; Gupta, Archika; Pandey, Anand; Kureel, Shiv Narain

    2016-01-01

    Acute abdomen in dengue, a common arboviral disease found in tropical and subtropical countries, is not uncommon and can occasionally present as acute surgical emergency requiring urgent surgical intervention. The spectrum of acute abdomen presenting as surgical emergency in dengue infection that raises suspicion of an abdominal catastrophe includes acute appendicitis, acute cholecystitis, appendicitis and, rarely, intestinal perforation. All cases of intestinal perforation including appendicular, gastric and jejunal perforation have been reported in adult patients during the course of dengue infection. However, intestinal perforation during the course of dengue infection in the paediatric age group has never been reported. We report two cases of ileal perforation in children occurring during the course of dengue infection. PMID:27485879

  7. Dengue Virus Infection-Enhancing Activity in Serum Samples with Neutralizing Activity as Determined by Using FcγR-Expressing Cells

    PubMed Central

    Moi, Meng Ling; Lim, Chang-Kweng; Chua, Kaw Bing; Takasaki, Tomohiko; Kurane, Ichiro

    2012-01-01

    Background Progress in dengue vaccine development has been hampered by limited understanding of protective immunity against dengue virus infection. Conventional neutralizing antibody titration assays that use FcγR-negative cells do not consider possible infection-enhancement activity. We reasoned that as FcγR-expressing cells are the major target cells of dengue virus, neutralizing antibody titration assays using FcγR-expressing cells that determine the sum of neutralizing and infection-enhancing activity, may better reflect the biological properties of antibodies in vivo. Methods and Findings We evaluated serum samples from 80 residents of a dengue endemic country, Malaysia, for neutralizing activity, and infection-enhancing activity at 1∶10 serum dilution by using FcγR-negative BHK cells and FcγR-expressing BHK cells. The serum samples consisted of a panel of patients with acute DENV infection (31%, 25/80) and a panel of donors without acute DENV infection (69%, 55/80). A high proportion of the tested serum samples (75%, 60/80) demonstrated DENV neutralizing activity (PRNT50≥10) and infection-enhancing activity. Eleven of 18 serum samples from patients with acute secondary DENV infection demonstrated neutralizing activity to the infecting serotype determined by using FcγR-negative BHK cells (PRNT50≥10), but not when determined by using FcγR-expressing cells. Conclusion Human serum samples with low neutralizing activity determined by using FcγR-negative cells showed DENV infection-enhancing activity using FcγR-expressing cells, whereas those with high neutralizing activity determined by using FcγR-negative cells demonstrate low or no infection-enhancing activity using FcγR-expressing cells. The results suggest an inverse relationship between neutralizing antibody titer and infection-enhancing activity, and that neutralizing activity determined by using FcγR-expressing cells, and not the activity determined by using FcγR-negative cells, may

  8. 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

  9. Dysregulated Serum MiRNA Profile and Promising Biomarkers in Dengue-infected Patients

    PubMed Central

    Ouyang, Xiaoxi; Jiang, Xin; Gu, Dayong; Zhang, Yaou; Kong, S.K.; Jiang, Chaoxin; Xie, Weidong

    2016-01-01

    Objectives: Pathological biomarkers and mechanisms of dengue infection are poorly understood. We investigated a new serum biomarker using miRNAs and performed further correlation analysis in dengue-infected patients. Methods: Expression levels of broad-spectrum miRNAs in serum samples from three patients with dengue virus type 1 (DENV-1) and three healthy volunteers were separately analyzed using miRNA PCR arrays. The expressions of the five selected miRNAs were verified by qRT-PCR in the sera of 40 DENV-1 patients and compared with those from 32 healthy controls. Receiver operating characteristic (ROC) curve and correlation analyses were performed to evaluate the potential of these miRNAs for the diagnosis of dengue infection. Results: MiRNA PCR arrays revealed that 41 miRNAs were upregulated, whereas 12 miRNAs were down-regulated in the sera of DENV-1 patients compared with those in healthy controls. Among these miRNAs, qRT-PCR validation showed that serum hsa-miR-21-5p, hsa-miR-590-5p, hsa-miR-188-5p, and hsa-miR-152-3p were upregulated, whereas hsa-miR-146a-5p was down-regulated in dengue-infected patients compared with healthy controls. ROC curves showed serum hsa-miR-21-5p and hsa-miR-146a-5p could distinguish dengue-infected patients with preferable sensitivity and specificity. Correlation analysis indicated that expression levels of serum hsa-miR-21-5p and hsa-miR-146a-5p were negative and positively correlated with the number of white blood cells and neutrophils, respectively. Functional analysis of target proteins of these miRNAs in silico indicated their involvement in inflammation and cell proliferation. Conclusion: Dengue-infected patients have a broad “fingerprint” profile with dysregulated serum miRNAs. Among these miRNAs, serum hsa-miR-21-5p, hsa-miR-146a-5p, hsa-miR-590-5p, hsa-miR-188-5p, and hsa-miR-152-3p were identified as promising serum indicators for dengue infection. PMID:26941580

  10. Dengue Virus Infection of Mast Cells Triggers Endothelial Cell Activation ▿

    PubMed Central

    Brown, Michael G.; Hermann, Laura L.; Issekutz, Andrew C.; Marshall, Jean S.; Rowter, Derek; Al-Afif, Ayham; Anderson, Robert

    2011-01-01

    Vascular perturbation is a hallmark of severe forms of dengue disease. We show here that antibody-enhanced dengue virus infection of primary human cord blood-derived mast cells (CBMCs) and the human mast cell-like line HMC-1 results in the release of factor(s) which activate human endothelial cells, as evidenced by increased expression of the adhesion molecules ICAM-1 and VCAM-1. Endothelial cell activation was prevented by pretreatment of mast cell-derived supernatants with a tumor necrosis factor (TNF)-specific blocking antibody, thus identifying TNF as the endothelial cell-activating factor. Our findings suggest that mast cells may represent an important source of TNF, promoting vascular endothelial perturbation following antibody-enhanced dengue virus infection. PMID:21068256

  11. Mosquito-borne infections in Fiji. V. The 1971-73 dengue epidemic.

    PubMed

    Maguire, T; Miles, J A; Macnamara, F N; Wilkinson, P J; Austin, F J; Mataika, J U

    1974-10-01

    A dengue epidemic due to type 2 virus involving some 3,400 cases began in Fiji early in 1971, had a peak during May, June and July, and cases have continued to occur with a low incidence during 1972 and 1973. Many of the notified cases showed classical dengue fever symptoms and there were no confirmed cases of haemorrhagic fever. A serological survey indicated that there had been at least 20,000 subclinical infections. It is probable that the virus was introduced to Fiji either through the port of Lautoka or Nadi international airport in February 1971. The normal travel patterns of residents must have spread the virus to all the more accessible localities but, with the exception of Rotuma, it caused infections only in areas where Aedes aegypti was available as a vector. There was no evidence that pre-existing dengue type 1 serum antibody gave any protection during this epidemic.

  12. 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.

  13. 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.

  14. Oxidative stress in severe dengue viral infection: association of thrombocytopenia with lipid peroxidation.

    PubMed

    Soundravally, R; Sankar, P; Bobby, Z; Hoti, S L

    2008-09-01

    Oxidative stress in viral infections has been suggested. The study was carried out to assess the oxidative stress in the different clinical spectrums of dengue infection and to evaluate if thrombocytopenia is associated with lipid and protein oxidative injury. Twenty-seven dengue fever (DF), 32 dengue hemorrhagic fever (DHF) and 21 dengue shock syndrome (DSS) cases were studied at 3, 5 and 7 days of illness. Sixty-three healthy subjects were selected as controls. Serum protein carbonyls (PCOs), malendialdehyde (MDA) and total antioxidant status (TAS) were estimated in blood. Dengue infected individuals had significantly high levels of PCOs and MDA on the three days tested in comparison to controls. In DF cases, no significant changes in the levels of MDA and PCOs were found in course of time. However, among DHF and DSS, significant increase in MDA levels was found in the fifth and seventh day samples in comparison to their respective third day sample (P < 0.05). Using one way ANOVA, high PCOs levels were found in DSS in comparison to DF and DHF cases on all the three days tested (P < 0.001). TAS levels were found to be low among DSS on days 5 and 7 and day 7 in DHF when compared with DF cases. Correlation analysis between MDA and hematocrit revealed a significant positive association between them in DHF and DSS on day 5 (DHF r = 0.372; p = 0.024 and DSS r = 0.535; p = 0.0-01) and day 7 (DHF r = 0.412; p = 0.003 and DSS r = 0.765; p < 0.0001). There was an important negative correlation between platelet count and plasma lipid peroxidation levels among DHF and DSS on all three days tested [day 3 (DHF r = -0.392; p = 0.012 and DSS r = -0.453; p = 0.004), day 5 (DHF r = -0.592; p < 0.001 and DSS r = -0.581; p < 0.001) and day 7 (DHF r = -0.418; p = 0.001 and DSS r = -0.515; p = 0.002)]. This study concludes that an increase in oxidative stress was found in dengue viral infection. The level of oxidative stress was maximal in DSS followed by DHF and its severity was

  15. Simple Clinical and Laboratory Predictors of Chikungunya versus Dengue Infections in Adults

    PubMed Central

    Lee, Vernon J.; Chow, Angela; Zheng, Xiaohui; Carrasco, Luis R.; Cook, Alex R.; Lye, David C.; Ng, Lee-Ching; Leo, Yee-Sin

    2012-01-01

    Background Dengue and chikungunya are co-circulating vector-borne diseases with substantial overlap in clinical presentations. It is important to differentiate between them during first presentation as their management, especially for dengue hemorrhagic fever (DHF), is different. This study compares their clinical presentation in Singapore adults to derive predictors to assist doctors in diagnostic decision-making. Methods We compared 117 patients with chikungunya infection diagnosed with reverse transcription-polymerase chain reaction (RT-PCR) with 917 dengue RT-PCR-positive adult patients (including 55 with DHF). We compared dengue fever (DF), DHF, and chikungunya infections by evaluating clinical characteristics of dengue and chikungunya; developing classification tools via multivariate logistic regression models and classification trees of disease etiology using clinical and laboratory factors; and assessing the time course of several clinical variables. Findings At first presentation to hospital, significantly more chikungunya patients had myalgia or arthralgia, and fewer had a sore throat, cough (for DF), nausea, vomiting, diarrhea, abdominal pain, anorexia or tachycardia than DF or DHF patients. From the decision trees, platelets <118×109/L was the only distinguishing feature for DF versus chikungunya with an overall correct classification of 89%. For DHF versus chikungunya using platelets <100×109/L and the presence of bleeding, the overall correct classification was 98%. The time course analysis supported platelet count as the key distinguishing variable. Interpretation There is substantial overlap in clinical presentation between dengue and chikungunya infections, but simple clinical and laboratory variables can predict these infections at presentation for appropriate management. PMID:23029573

  16. Dengue haemorrhagic fever and dengue shock syndrome: are they tumour necrosis factor-mediated disorders?

    PubMed

    Yadav, M; Kamath, K R; Iyngkaran, N; Sinniah, M

    1991-12-01

    A consecutive series of 24 patients with clinical features of primary dengue infection and 22 controls (14 patients with viral fever of unknown origin and 8 healthy subjects) were assayed for serum levels of tumour necrosis factor (TNF). The acute sera of the 24 patients with clinical dengue infection were positive for dengue virus-specific IgM antibody. Clinically, 8 had dengue fever (DF), 14 dengue haemorrhagic fever (DHF) and 2 dengue shock syndrome (DSS). All 16 patients with DHF/DSS had significantly elevated serum TNF levels but the 8 DF patients had TNF levels equivalent to that in the 22 controls. A case is made for augmented TNF production having a role for the pathophysiological changes observed in DHF/DSS and mediator modulation as a possible therapeutic approach to treatment.

  17. Novel vaccination approach for dengue infection based on recombinant immune complex universal platform.

    PubMed

    Kim, Mi-Young; Reljic, Rajko; Kilbourne, Jacquelyn; Ceballos-Olvera, Ivonne; Yang, Moon-Sik; Reyes-del Valle, Jorge; Mason, Hugh S

    2015-04-01

    Dengue infection is on the rise in many endemic areas of the tropics. Vaccination remains the most realistic strategy for prevention of this potentially fatal viral disease but there is currently no effective vaccine that could protect against all four known serotypes of the dengue virus. This study describes the generation and testing of a novel vaccination approach against dengue based on recombinant immune complexes (RIC). We modelled the dengue RIC on the existing Ebola RIC (Phoolcharoen, et al. Proc Natl Acad Sci USA 2011;108(Dec (51)):20695) but with a key modification that allowed formation of a universal RIC platform that can be easily adapted for use for other pathogens. This was achieved by retaining only the binding epitope of the 6D8 ant-Ebola mAb, which was then fused to the consensus dengue E3 domain (cEDIII), resulting in a hybrid dengue-Ebola RIC (DERIC). We expressed human and mouse versions of these molecules in tobacco plants using a geminivirus-based expression system. Following purification from the plant extracts by protein G affinity chromatography, DERIC bound to C1q component of complement, thus confirming functionality. Importantly, following immunization of mice, DERIC induced a potent, virus-neutralizing anti-cEDIII humoral immune response without exogenous adjuvants. We conclude that these self-adjuvanting immunogens have the potential to be developed as a novel vaccine candidate for dengue infection, and provide the basis for a universal RIC platform for use with other antigens. PMID:25728317

  18. Commercial Dengue Rapid Diagnostic Tests for Point-of-Care Application: Recent Evaluations and Future Needs?

    PubMed Central

    Blacksell, Stuart D.

    2012-01-01

    Dengue fever, dengue haemorrhagic fever, and dengue shock syndrome (DF/DHF/DSS) are tropical diseases that cause significant humanitarian and economic hardship. It is estimated that more than 2.5 billion people are at risk of infection and more than 100 countries have endemic dengue virus transmission. Laboratory tests are essential to provide an accurate diagnosis of dengue virus infection so that appropriate treatment and patient management may be administered. In many dengue endemic settings, laboratory diagnostic resources are limited and simple rapid diagnostic tests (RDTs) provide opportunities for point-of-care diagnosis. This paper addresses current issues relating to the application of commercial dengue RDTs for the diagnosis of acute dengue virus infection, recent diagnostic evaluations, and identifies future needs. PMID:22654479

  19. Commercial dengue rapid diagnostic tests for point-of-care application: recent evaluations and future needs?

    PubMed

    Blacksell, Stuart D

    2012-01-01

    Dengue fever, dengue haemorrhagic fever, and dengue shock syndrome (DF/DHF/DSS) are tropical diseases that cause significant humanitarian and economic hardship. It is estimated that more than 2.5 billion people are at risk of infection and more than 100 countries have endemic dengue virus transmission. Laboratory tests are essential to provide an accurate diagnosis of dengue virus infection so that appropriate treatment and patient management may be administered. In many dengue endemic settings, laboratory diagnostic resources are limited and simple rapid diagnostic tests (RDTs) provide opportunities for point-of-care diagnosis. This paper addresses current issues relating to the application of commercial dengue RDTs for the diagnosis of acute dengue virus infection, recent diagnostic evaluations, and identifies future needs.

  20. Human immune responses to dengue virus infection: lessons learned from prospective cohort studies.

    PubMed

    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.

  1. Activation of peripheral blood mononuclear cells by dengue virus infection depotentiates balapiravir.

    PubMed

    Chen, Yen-Liang; Abdul Ghafar, Nahdiyah; Karuna, Ratna; Fu, Yilong; Lim, Siew Pheng; Schul, Wouter; Gu, Feng; Herve, Maxime; Yokohama, Fumiaki; Wang, Gang; Cerny, Daniela; Fink, Katja; Blasco, Francesca; Shi, Pei-Yong

    2014-02-01

    In a recent clinical trial, balapiravir, a prodrug of a cytidine analog (R1479), failed to achieve efficacy (reducing viremia after treatment) in dengue patients, although the plasma trough concentration of R1479 remained above the 50% effective concentration (EC(50)). Here, we report experimental evidence to explain the discrepancy between the in vitro and in vivo results and its implication for drug development. R1479 lost its potency by 125-fold when balapiravir was used to treat primary human peripheral blood mononuclear cells (PBMCs; one of the major cells targeted for viral replication) that were preinfected with dengue virus. The elevated EC(50) was greater than the plasma trough concentration of R1479 observed in dengue patients treated with balapiravir and could possibly explain the efficacy failure. Mechanistically, dengue virus infection triggered PBMCs to generate cytokines, which decreased their efficiency of conversion of R1479 to its triphosphate form (the active antiviral ingredient), resulting in decreased antiviral potency. In contrast to the cytidine-based compound R1479, the potency of an adenosine-based inhibitor of dengue virus (NITD008) was much less affected. Taken together, our results demonstrate that viral infection in patients before treatment could significantly affect the conversion of the prodrug to its active form; such an effect should be calculated when estimating the dose efficacious for humans.

  2. Inflammatory mediators in dengue virus infection in children: interleukin-8 and its relationship to neutrophil degranulation.

    PubMed

    Juffrie, M; van Der Meer, G M; Hack, C E; Haasnoot, K; Sutaryo; Veerman, A J; Thijs, L G

    2000-02-01

    The chemokine interleukin-8 (IL-8) has chemoattractant activity for neutrophils and is able to activate and degranulate these cells. We investigated whether IL-8 may exert these effects in children with dengue virus infection. Circulating levels of IL-8, neutrophilic elastase (a constituent of the azurophilic granula of neutrophils), and lactoferrin, released from specific granula, were measured in 186 children with dengue virus infection, 33 healthy children as negative controls and 11 children with bacterial infections as positive controls. Levels of IL-8 on admission were elevated in 71% of the dengue patients, while the elastase and lactoferrin levels were increased in 68 and 17% of patients, respectively. These levels were significantly higher than in healthy children (P < 0.05) for IL-8 and elastase but not for lactoferrin (by the Wilcoxon-Mann-Whitney [WMW] U test). Similar levels of IL-8 were found in patients with bacterial infections. Levels of IL-8 and elastase in patients with shock were significantly higher than in patients without shock (P = 0.02; WMW), but those of lactoferrin were not. IL-8 correlated with elastase and lactoferrin (r = 0.19 and P = 0.009 versus r = 0.24 and P = 0.001, respectively; two-tailed Spearman rank correlation). Thus, IL-8 levels are increased in most patients with dengue virus infection and correlate with degranulation of neutrophils as well as with some clinical and hemodynamic variables. These findings suggest a role for IL-8 in the pathogenesis of dengue virus infection.

  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. Domestic dengue infection with hemophagocytic lymphohistiocytosis successfully treated by early steroid therapy.

    PubMed

    Yoshifuji, Kota; Oshina, Takahiro; Sonokawa, Saeko; Noguchi, Yuma; Suzuki, Sayaka; Tanaka, Keisuke; Kumagai, Takashi

    2016-07-01

    A 34-year-old man, working at a park in Tokyo, Japan, was repeatedly bitten by mosquitoes while cutting grass. He was hospitalized with sudden fever, fatigue, and weakness. He was eventually diagnosed with dengue virus infection, detected using reverse transcription polymerase chain reaction for the genome and by the presence of nonstructural protein 1 in his peripheral blood. Symptomatic treatments such as acetaminophen for the fever were not effective. Moreover, peripheral blood examination showed drastically decreased white blood cells and platelets, as well as marked elevations of ferritin and soluble interleukin 2 receptor. Furthermore, bone marrow examination revealed increased macrophages with hemophagocytosis. Dengue infection with hemophagocytic lymphohistiocytosis (HLH) was ultimately diagnosed. Half-dose steroid pulse therapy for three days dramatically reduced his temperature, thereby ameliorating physical symptoms and restoring normal peripheral blood data. He was discharged 12 days after admission. Dengue infection with HLH is rare and this is the first report, to our knowledge, of domestic dengue infection with HLH in Japan. Early steroid therapy may be effective in such cases. PMID:27498730

  5. 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.

  6. Dengue: an emerging disease in Nepal.

    PubMed

    Pun, S B

    2011-01-01

    Dengue is an acute infectious disease caused by dengue viruses and transmitted by the Aedes species of mosquito. The rapid global spread of the dengue virus into new areas has begun to attract more research attention. A series of dengue fever outbreaks in several districts of Nepal has been recently observed. The evidence of all four serotypes (DEN - 1 - 4) could be a consequence of a sudden resurgence of a more severe dengue disease in Nepal. Health care providers need to become familiar with the disease to prevent or control the possibility of future outbreaks. The clinical features, diagnosis, treatment, epidemiological patterns and challenges of dengue virus infection in Nepal will be discussed here.

  7. Mast cell–macrophage dynamics in modulation of dengue virus infection in skin

    PubMed Central

    Chu, Ya-Ting; Wan, Shu-Wen; Anderson, Robert; Lin, Yee-Shin

    2015-01-01

    Dengue virus (DENV) infection causes dengue fever, dengue haemorrhagic fever, or dengue shock syndrome. Mast cells have been speculated to play a role in DENV disease although their precise roles are unclear. In this study, we used mast cell-deficient KitW-sh/W-sh mice to investigate the involvement of mast cells after intradermal DENV infection. An approximately two- to three-fold higher level of DENV NS3 antigen was detected at the skin inoculation site in DENV-infected KitW-sh/W-sh mice than in DENV-infected wild-type (WT) mice (using a dose of 1 × 109 plaque-forming units/mouse). Moreover, as an indicator of heightened pathogenesis, a more prolonged bleeding time was observed in DENV-infected KitW-sh/W-sh mice than in WT mice. Monocytes/macrophages are considered to be important targets for DENV infection, so we investigated the susceptibility and chemokine response of DENV-infected peritoneal macrophages from KitW-sh/W-sh and WT mice both ex vivo and in vivo. There was a tendency for higher DENV infection and higher secretion of CCL2 (MCP-1) from peritoneal macrophages isolated from KitW-sh/W-sh mice than those from WT mice. In vivo studies using intradermal inoculation of DENV showed about twofold higher levels of infiltrating macrophages and CCL2 (MCP-1) at the inoculation site in both mock control and DENV-inoculated KitW-sh/W-sh mice than in corresponding WT mice. In summary, compared with WT mice, KitW-sh/W-sh mice show enhanced DENV infection and macrophage infiltration at the skin inoculation site as well as increased DENV-associated bleeding time. The results indicate an intriguing interplay between mast cells and tissue macrophages to restrict DENV replication in the skin. PMID:26059780

  8. Mast cell-macrophage dynamics in modulation of dengue virus infection in skin.

    PubMed

    Chu, Ya-Ting; Wan, Shu-Wen; Anderson, Robert; Lin, Yee-Shin

    2015-09-01

    Dengue virus (DENV) infection causes dengue fever, dengue haemorrhagic fever, or dengue shock syndrome. Mast cells have been speculated to play a role in DENV disease although their precise roles are unclear. In this study, we used mast cell-deficient Kit(W-sh/W-sh) mice to investigate the involvement of mast cells after intradermal DENV infection. An approximately two- to three-fold higher level of DENV NS3 antigen was detected at the skin inoculation site in DENV-infected Kit(W-sh/W-sh) mice than in DENV-infected wild-type (WT) mice (using a dose of 1 × 10(9) plaque-forming units/mouse). Moreover, as an indicator of heightened pathogenesis, a more prolonged bleeding time was observed in DENV-infected Kit(W-sh/W-sh) mice than in WT mice. Monocytes/macrophages are considered to be important targets for DENV infection, so we investigated the susceptibility and chemokine response of DENV-infected peritoneal macrophages from Kit(W-sh/W-sh) and WT mice both ex vivo and in vivo. There was a tendency for higher DENV infection and higher secretion of CCL2 (MCP-1) from peritoneal macrophages isolated from Kit(W-sh/W-sh) mice than those from WT mice. In vivo studies using intradermal inoculation of DENV showed about twofold higher levels of infiltrating macrophages and CCL2 (MCP-1) at the inoculation site in both mock control and DENV-inoculated Kit(W-sh/W-sh) mice than in corresponding WT mice. In summary, compared with WT mice, Kit(W-sh/W-sh) mice show enhanced DENV infection and macrophage infiltration at the skin inoculation site as well as increased DENV-associated bleeding time. The results indicate an intriguing interplay between mast cells and tissue macrophages to restrict DENV replication in the skin.

  9. 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

  10. 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.

  11. B cells naturally induced during dengue virus infection release soluble CD27, the plasma level of which is associated with severe forms of pediatric dengue.

    PubMed

    Castañeda, Diana M; Salgado, Doris M; Narváez, Carlos F

    2016-10-01

    The CD27 and CD38 antigens are highly expressed on the plasmablast surface, and a massive plasmablast response has been described for dengue virus infection. Soluble CD27 and CD38 forms (sCD27 and sCD38, respectively) increase after immune activation. Here, we show increased sCD27 release in cultures of purified polyclonally stimulated B cells. T and B cells isolated from children with dengue spontaneously produced higher levels of sCD27 but not sCD38, compared with healthy children (P=0.03), and sCD27 levels positively correlated with plasmablast frequency in the cultures (rho=0.58, P=0.01). Children with dengue had higher plasma levels of sCD27 and sCD38 than healthy children, which decreased during convalescence. Plasma sCD27 was higher in severe than with mild dengue, but the opposite was observed for sCD38. These findings support a potential new role for B cells in dengue pathogenesis, and sCD27 and sCD38 are novel biomarkers associated with clinical outcome during dengue virus infection.

  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. 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)

  14. 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.

  15. Seroprevalence of past dengue virus infection among children and adolescents in Singapore.

    PubMed

    Ang, Li Wei; Cutter, Jeffery; James, Lyn; Goh, Kee Tai

    2015-12-01

    We conducted a pediatric seroprevalence study of dengue virus (DENV) infection in Singapore, a dengue endemic city-state. Residual sera from 1,200 Singapore residents aged 1-17 years seen in two hospitals between 2008 and 2010 were tested for anti-DENV IgG antibodies. The overall seroprevalence was 10.4% (95%CI: 8.7-12.1%). There had been a marked decline in seroprevalence in the 15-19-year age group over the last three decades, while the prevalence in the 1-5-year olds (12.6%) was significantly higher than that of the 1996-1997 pediatric survey (0.8%). The overall dengue seroprevalence in children and adolescents remained low.

  16. Fatal dengue hemorrhagic fever imported into Germany.

    PubMed

    Schmidt-Chanasit, J; Tenner-Racz, K; Poppert, D; Emmerich, P; Frank, C; Dinges, C; Penning, R; Nerlich, A; Racz, P; Günther, S

    2012-08-01

    Dengue virus (DENV) is an arthropod-borne virus (family Flaviviridae) causing dengue fever or dengue hemorrhagic fever. Here, we report the first fatal DENV infection imported into Germany. A female traveler was hospitalized with fever and abdominal pain after returning from Ecuador. Due to a suspected acute acalculous cholecystitis, cholecystectomy was performed. After cholecystectomy, severe spontaneous bleeding from the abdominal wound occurred and the patient died. Postmortem analysis of transudate and tissue demonstrated a DENV secondary infection of the patient and a gallbladder wall thickening (GBWT) due to an extensive edema.

  17. Gene Polymorphisms and Serum Levels of Pro- and Anti-Inflammatory Markers in Dengue Viral Infections.

    PubMed

    Feitosa, Rosimar Neris Martins; Vallinoto, Antonio Carlos Rosário; Vasconcelos, Pedro Fernando da Costa; Azevedo, Raimunda do Socorro da Silva; Azevedo, Vânia Nakauth; Machado, Luiz Fernando Almeida; Lima, Sandra Souza; Ishak, Marluísa de Oliveira Guimarães; Ishak, Ricardo

    2016-09-01

    Pro- and anti-inflammatory markers (tumor necrosis factor [TNF]-α, TNF-β, interferon [IFN]-γ, interleukin [IL]-6, IL-8, IL-10, and C-reactive protein [CRP]) were investigated in 80 patients infected with dengue viruses, 100 patients presenting with febrile illness but negative for dengue, and 99 healthy subjects. Immunoenzyme methods were used for quantitative assays in the plasma. Polymorphisms of TNF-α, TNF-β, IL-6, IL-8, and IL-10 genes were assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific oligonucleotide (ASO)-PCR for the IFN-γ. The highest mean serum levels of TNF-α, IFN-γ, IL-8, and CRP were observed in dengue-positive individuals. TNF-β, IL-6, and IL-10 levels were significantly higher in the dengue-negative individuals. No cytokine expression pattern was evidenced according to virus serotype. Genotypic frequency distributions were statistically significant for the polymorphisms of TNF-α and IFN-γ among positive, negative, and control dengue groups and IFN-γ among groups DENV-1, DENV-2, DENV-3, and controls. Modulation of cytokine expression and polymorphisms is a complex matter and needs further explanation considering the ethnic origins of the Brazilian population.

  18. Gene Polymorphisms and Serum Levels of Pro- and Anti-Inflammatory Markers in Dengue Viral Infections.

    PubMed

    Feitosa, Rosimar Neris Martins; Vallinoto, Antonio Carlos Rosário; Vasconcelos, Pedro Fernando da Costa; Azevedo, Raimunda do Socorro da Silva; Azevedo, Vânia Nakauth; Machado, Luiz Fernando Almeida; Lima, Sandra Souza; Ishak, Marluísa de Oliveira Guimarães; Ishak, Ricardo

    2016-09-01

    Pro- and anti-inflammatory markers (tumor necrosis factor [TNF]-α, TNF-β, interferon [IFN]-γ, interleukin [IL]-6, IL-8, IL-10, and C-reactive protein [CRP]) were investigated in 80 patients infected with dengue viruses, 100 patients presenting with febrile illness but negative for dengue, and 99 healthy subjects. Immunoenzyme methods were used for quantitative assays in the plasma. Polymorphisms of TNF-α, TNF-β, IL-6, IL-8, and IL-10 genes were assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific oligonucleotide (ASO)-PCR for the IFN-γ. The highest mean serum levels of TNF-α, IFN-γ, IL-8, and CRP were observed in dengue-positive individuals. TNF-β, IL-6, and IL-10 levels were significantly higher in the dengue-negative individuals. No cytokine expression pattern was evidenced according to virus serotype. Genotypic frequency distributions were statistically significant for the polymorphisms of TNF-α and IFN-γ among positive, negative, and control dengue groups and IFN-γ among groups DENV-1, DENV-2, DENV-3, and controls. Modulation of cytokine expression and polymorphisms is a complex matter and needs further explanation considering the ethnic origins of the Brazilian population. PMID:27336361

  19. Dengue virus infection in Croatia: seroprevalence and entomological study.

    PubMed

    Pem-Novosel, Iva; Vilibic-Cavlek, Tatjana; Gjenero-Margan, Ira; Kaic, Bernard; Babic-Erceg, Andrea; Merdic, Enrih; Medic, Alan; Ljubic, Miljenko; Pahor, Djana; Erceg, Marijan

    2015-01-01

    During 2011-2012, a total of 1,180 sera samples were collected from residents of seven Croatian counties located on the Adriatic Coast and four counties in northeastern Croatia and tested for the presence of dengue virus (DENV) IgG antibodies using ELISA. Reactive samples were further tested by IFA. Seven samples (0.59%) tested positive for DENV antibodies. Seroprevalence rates by county varied from 0-2.21%. The highest seropositivity rate (2.21%) was found in the Dubrovnik-Neretva County where autochthonous dengue cases were recorded in 2010. Additionally,3,699 mosquitoes were collected from 126 localities along the Adriatic coast in August-September, 2011. Aedes albopictus was the most prevalent species (81.37%). No evidence of DENV RNA was detected by RT-PCR among 1,748 female mosquitoes.

  20. 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

  1. A global airport-based risk model for the spread of dengue infection via the air transport network.

    PubMed

    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.

  2. Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4.

    PubMed

    Schaeffer, Evelyne; Flacher, Vincent; Papageorgiou, Vasiliki; Decossas, Marion; Fauny, Jean-Daniel; Krämer, Melanie; Mueller, Christopher G

    2015-07-01

    Dengue virus (DENV) is responsible for the most prevalent arthropod-borne viral infection in humans. Events decisive for disease development occur in the skin after virus inoculation by the mosquito. Yet, the role of human dermis-resident immune cells in dengue infection and disease remains elusive. Here we investigated how dermal dendritic cells (dDCs) and macrophages (dMs) react to DENV and impact on immunopathology. We show that both CD1c(+) and CD14(+) dDC subsets were infected, but viral load greatly increased in CD14(+) dDCs upon IL-4 stimulation, which correlated with upregulation of virus-binding lectins Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Nonintegrin (DC-SIGN/CD209) and mannose receptor (CD206). IL-4 also enhanced T-cell activation by dDCs, which was further increased upon dengue infection. dMs purified from digested dermis were initially poorly infected but actively replicated the virus and produced TNF-α upon lectin upregulation in response to IL-4. DC-SIGN(+) cells are abundant in inflammatory skin with scabies infection or Th2-type dermatitis, suggesting that skin reactions to mosquito bites heighten the risk of infection and subsequent immunopathology. Our data identify dDCs and dMs as primary arbovirus target cells in humans and suggest that dDCs initiate a potent virus-directed T-cell response, whereas dMs fuel the inflammatory cascade characteristic of dengue fever. PMID:25521455

  3. Determination of viremia and concentration of circulating nonstructural protein 1 in patients infected with dengue virus in Mexico.

    PubMed

    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

    2013-03-01

    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.

  4. 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.

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

    PubMed

    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

  6. 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

  7. Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection.

    PubMed

    Chan, Kuan Rong; Zhang, Summer Li-Xin; Tan, Hwee Cheng; Chan, Ying Kai; Chow, Angelia; Lim, Angeline Pei Chiew; Vasudevan, Subhash G; Hanson, Brendon J; Ooi, Eng Eong

    2011-07-26

    The interaction of antibodies, dengue virus (DENV), and monocytes can result in either immunity or enhanced virus infection. These opposing outcomes of dengue antibodies have hampered dengue vaccine development. Recent studies have shown that antibodies neutralize DENV by either preventing virus attachment to cellular receptors or inhibiting viral fusion intracellularly. However, whether the antibody blocks attachment or fusion, the resulting immune complexes are expected to be phagocytosed by Fc gamma receptor (FcγR)-bearing cells and cleared from circulation. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcγR-mediated uptake by monocytes whereas other antibodies would have resulted in enhancement of DENV replication. Using convalescent sera from dengue patients, we observed that neutralization of the homologous serotypes occurred despite FcγR-mediated uptake. However, FcγR-mediated uptake appeared to be inhibited when neutralized heterologous DENV serotypes were used instead. We demonstrate that this inhibition occurred through the formation of viral aggregates by antibodies in a concentration-dependent manner. Aggregation of viruses enabled antibodies to cross-link the inhibitory FcγRIIB, which is expressed at low levels but which inhibits FcγR-mediated phagocytosis and hence prevents antibody-dependent enhancement of DENV infection in monocytes. PMID:21746897

  8. Household survey of dengue infection in central Brazil: spatial point pattern analysis and risk factors assessment.

    PubMed

    Siqueira, João B; Martelli, Celina M T; Maciel, Ivan J; Oliveira, Renato M; Ribeiro, Maria G; Amorim, Flúvia P; Moreira, Bruno C; Cardoso, Divina D P; Souza, Wayner V; Andrade, Ana Lúcia S S

    2004-11-01

    Urban dengue fever is now considered a major public health threat in most American countries. A household survey was conducted in the city of Goiania in central Brazil in 2001 to assess prevalence of dengue infection and individual and area-based risk factors. Spatial point pattern analysis was performed using the dual Kernel method. A total of 1,610 households were surveyed; 1,585 individuals more than five years old had blood and data collected. Sera were tested for IgM/IgG antibodies by an enzyme-linked immunoassay. Area-based indicators derived from census data were linked to geocoded residential address. The seroprevalence of dengue was 29.5% and the estimate prevalence surface reached 50% in the outskirts areas. The risk of infection was significantly associated with older age (P < 0.01), low education (odds ratio [OR] = 3.45, 95% confidence interval [CI] = 1.82-6.55), and low income (OR = 1.32, 95% CI = 1.02-1.71) in multivariate analysis. This study highlighted the heterogeneity of dengue transmission within the city and can assist in spatial targeting control interventions.

  9. Dengue conundrums.

    PubMed

    Gibbons, Robert V

    2010-11-01

    Dengue virus is the most common arboviral infection of humans in the tropical and subtropical regions of the world. This review briefly describes some of the challenges it presents. Dengue is an emerging disease; it is increasing in geographical distribution and severity, despite being significantly underreported. The World Health Organization case definition for the generally more severe manifestation of infection, dengue haemorrhagic fever (DHF), is controversial. The name DHF is something of a misnomer as the disease infrequently results in frank haemorrhage; the hallmark of DHF is actually plasma leakage. The existence of four closely related dengue virus serotypes contributes to difficulties in diagnosis and to original antigenic sin in the serological response to infection. The existence of multiple serotypes can result in more severe disease upon a second infection and complicates vaccine development. Nevertheless, a safe and effective vaccine is the greatest prospect for stemming the tide of dengue.

  10. Acute Arboviral Infections in Guinea, West Africa, 2006

    PubMed Central

    Jentes, Emily S.; Robinson, Jaimie; Johnson, Barbara W.; Conde, Ibrahima; Sakouvougui, Yosse; Iverson, Jennifer; Beecher, Shanna; Bah, M. Alpha; Diakite, Fousseny; Coulibaly, Mamadi; Bausch, Daniel G.

    2010-01-01

    Acute febrile illnesses comprise the majority of the human disease burden in sub-Saharan Africa. We hypothesized that arboviruses comprised a considerable proportion of undiagnosed febrile illnesses in Guinea and sought to determine the frequency of arboviral disease in two hospitals there. Using a standard case definition, 47 suspected cases were detected in approximately 4 months. Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque-reduction neutralization assays revealed that 63% (30/47) of patients were infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8 chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the first reported cases of human disease from these viruses in Guinea and the first reported cases of symptomatic Tahyna infection in Africa. These results strongly suggest that arboviruses circulate and are common causes of disease in Guinea. Improving surveillance and laboratory capacity for arbovirus diagnoses will be integral to understanding the burden posed by these agents in the region. PMID:20682888

  11. Acute arboviral infections in Guinea, West Africa, 2006.

    PubMed

    Jentes, Emily S; Robinson, Jaimie; Johnson, Barbara W; Conde, Ibrahima; Sakouvougui, Yosse; Iverson, Jennifer; Beecher, Shanna; Bah, M Alpha; Diakite, Fousseny; Coulibaly, Mamadi; Bausch, Daniel G; Bryan, Juliet

    2010-08-01

    Acute febrile illnesses comprise the majority of the human disease burden in sub-Saharan Africa. We hypothesized that arboviruses comprised a considerable proportion of undiagnosed febrile illnesses in Guinea and sought to determine the frequency of arboviral disease in two hospitals there. Using a standard case definition, 47 suspected cases were detected in approximately 4 months. Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque-reduction neutralization assays revealed that 63% (30/47) of patients were infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8 chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the first reported cases of human disease from these viruses in Guinea and the first reported cases of symptomatic Tahyna infection in Africa. These results strongly suggest that arboviruses circulate and are common causes of disease in Guinea. Improving surveillance and laboratory capacity for arbovirus diagnoses will be integral to understanding the burden posed by these agents in the region.

  12. Diagnosis of dengue infection using various diagnostic tests in the early stage of illness.

    PubMed

    Lolekha, Rangsima; Chokephaibulkit, Kulkanya; Yoksan, Sutee; Vanprapar, Nirun; Phongsamart, Wanatpreeya; Chearskul, Sanay

    2004-06-01

    In order to elucidate the usefulness of various tests in the early course of dengue infection, in terms of diagnosis and correlation with clinical severity, blood specimens were collected every 48 hours on 3 occasions from patients with clinical suspicion of dengue infection with fever for less than 4 days. Viral isolation was attempted by mosquito inoculation (MI), tissue culture inoculation (TC), and reverse transcriptase polymerase chain reaction (RT-PCR). Antibodies were detected by hemagglutination inhibition test (HI), an in-house-ELISA (IH-ELISA), and an ELISA by MRL diagnostics Clinical data were collected from the time of enrollment to complete recovery. Of the 40 patients enrolled, 31 were diagnosed as dengue infection and confirmed by either serology or viral isolation. Of these, 12 had primary infection and 19 had secondary infection. Dengue fever occurred in 9 cases. Dengue viruses were isolated from 28 out of 31 patients, and dengue hemorrhagic fever was diagnosed in 22 patients. Viral serotypes identified by viral isolation, and RT-PCR were concordant: DEN1 was isolated in 8, DEN2 in 13, DEN3 in 5, and DEN4 in 2 patients. Viral isolation yielded positive results on blood collected before the 5th day of fever. MI was more sensitive than TC. RT-PCR was less sensitive than viral isolation during the early days of fever, but became more sensitive after the 5th day of fever. RT-PCR was able to detect virus up to day 7-8 of fever, even after defervescence, and in the presence of antibody. During the febrile stage, serological diagnosis on blood samples taken 48 hours apart was carried out by HI, IH-ELISA, and MRL-ELISA, facilitating diagnosis in 3 (10%), 21 (67%), and 27 (87%) of patients, respectively. All of the patients with secondary infection were diagnosed by MRL-ELISA before defervescence. By the 8th day of fever, a serological diagnosis aided to diagnose in 9 (29%), 29 (93%), and 31 (100%) of patients by HI, IH-ELISA, and MRL-ELISA, respectively

  13. 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

  14. Dengue Virus (DENV) Neutralizing Antibody Kinetics in Children After Symptomatic Primary and Postprimary DENV Infection.

    PubMed

    Clapham, Hannah E; Rodriguez-Barraquer, Isabel; Azman, Andrew S; Althouse, Benjamin M; Salje, Henrik; Gibbons, Robert V; Rothman, Alan L; Jarman, Richard G; Nisalak, Ananda; Thaisomboonsuk, Butsaya; Kalayanarooj, Siripen; Nimmannitya, Suchitra; Vaughn, David W; Green, Sharone; Yoon, In-Kyu; Cummings, Derek A T

    2016-05-01

    The immune response to dengue virus (DENV) infection is complex and not fully understood. Using longitudinal data from 181 children with dengue in Thailand who were followed for up to 3 years, we describe neutralizing antibody kinetics following symptomatic DENV infection. We observed that antibody titers varied by serotype, homotypic vs heterotypic responses, and primary versus postprimary infections. The rates of change in antibody titers over time varied between primary and postprimary responses. For primary infections, titers increased from convalescence to 6 months. By comparing homotypic and heterotypic antibody titers, we saw an increase in type specificity from convalescence to 6 months for primary DENV3 infections but not primary DENV1 infections. In postprimary cases, there was a decrease in titers from convalescence up until 6 months after infection. Beginning 1 year after both primary and postprimary infections, there was evidence of increasing antibody titers, with greater increases in children with lower titers, suggesting that antibody titers were boosted due to infection and that higher levels of neutralizing antibody may be more likely to confer a sterilizing immune response. These findings may help to model virus transmission dynamics and provide baseline data to support the development of vaccines and therapeutics.

  15. 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

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

    PubMed

    Lindsay, Michael D A; Jardine, Andrew; Giele, Carolien; Armstrong, Paul; McCarthy, Suzi; Whittle, Amanda; Pal, Naru; Lyttle, Heather; Harrington, Sue; Nicholson, Jay; Smith, David

    2015-09-01

    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.

  17. Status of circulating immune complexes, IL8 titers and cryoglobulins in patients with dengue infection.

    PubMed

    Patra, Goutam; Ghosh, Manab; Modak, Dolanchampa; Bandopadhyay, Bhaswati; Saha, Bibhuti; Mukhopadhyay, Sumi

    2015-11-01

    Dengue, a serious viral infection caused by the mosquito vector, Aedes aegyptii, affects about 390 million people annually from more than 125 countries across the globe. However, until now, there is no reliable clinical or laboratory indicator to accurately predict the development of dengue severity. Here, we explored critical pathophysiological determinants like IL8, circulating immune complex (CIC) and cryoglobulin in dengue-infected patients for identification of novel dengue severity biomarker(s). Totally, 100 clinically suspected dengue cases were tested by NS1 ELISA and MAC ELISA for dengue virus aetiology. For control, 49 healthy volunteers were included. Blood profiling (complete hemogram and liver function test) of patient population were done using automated cell counter and standard auto analyzer based biochemical analysis. Serum CIC was quantified by PEG precipitation. Serum cryoglobulins were estimated by Folin assay. Levels of serum IL-8 were assessed by standard sandwich ELISA kits. Patient CIC were further characterized by SDS Gel electrophoresis. Forty per cent of the cases tested positive, of which 11 patients had severe clinical manifestation. The mean ±SEM of cryoglobulin concentration for DHF, DF, and HC were 1.30 ± 0.31, 0.59 ± 0.08 and 0.143 ± 0.009 μg/μl, respectively. Thus, DHF and DF patients have shown 9- and 2.2-fold increase in cryoglobulin levels; and 18- and 5-fold increased CIC, respectively compared to HC patients. The mean ±SEM of CIC-PEG index for DHF, DF and HC were 491 ± 41.22, 146 ± 14.19 and 27.98 ± 2.56, respectively. Raised levels of IL8 titers were also found in all 11 DHF patients. Peak levels of CIC, cryoglobulin and IL8 titers were associated with thrombocytopenia. SDS PAGE analysis of CIC from DHF revealed the presence of at least six protein bands that were not observed in samples from DF and HC. Prediction efficacy of IL8, CIC and cryoglobulin for DHF was determined using the receiver operator characteristic

  18. 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

  19. Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure.

    PubMed

    Young, Park Chi; Hae, Chung Choon; Lee, Kim Hyun; Hoon, Chung Jong

    2003-12-01

    Rhabdomyolysis is a rare complication that emerges in a variety of infectious diseases, such as tsutsugamushi infection. In this study, we report a 71-year-old female patient with tsutsugamushi infection who exhibiting rhabdomyolysis and acute renal failure. On admission, an eschar, which is characteristic of tsutsugamushi infection, was found on her right flank area. Moreover, her tsutsugamushi antibody titer was 1:40960. The elevated values of serum creatinine phosphokinase (CPK), aldolase, creatinine and dark brown urine secondary to myoglobinuria are consistent with indications of rhabdomyolysis and acute renal failure due to tsutsugamushi infection. Her health improved without any residual effects after treatment with doxycyclin and hydration with normal saline. PMID:14717236

  20. Acute otitis media and respiratory virus infections.

    PubMed

    Ruuskanen, O; Arola, M; Putto-Laurila, A; Mertsola, J; Meurman, O; Viljanen, M K; Halonen, P

    1989-02-01

    We studied the association of acute otitis media with different respiratory virus infections in a pediatric department on the basis of epidemics between 1980 and 1985. Altogether 4524 cases of acute otitis media were diagnosed. The diagnosis was confirmed by tympanocentesis in 3332 ears. Respiratory virus infection was diagnosed during the same period in 989 patients by detecting viral antigen in nasopharyngeal mucus. There was a significant correlation between acute otitis media and respiratory virus epidemics, especially respiratory syncytial virus epidemics. There was no significant correlation between outbreaks of other respiratory viruses and acute otitis media. Acute otitis media was diagnosed in 57% of respiratory syncytial virus, 35% of influenza A virus, 33% of parainfluenza type 3 virus, 30% of adenovirus, 28% of parainfluenza type 1 virus, 18% of influenza B virus and 10% of parainfluenza type 2 virus infections. These observations show a clear association of respiratory virus infections with acute otitis media. In this study on hospitalized children Haemophilus influenzae strains were the most common bacteriologic pathogens in middle ear fluid, occurring in 19% of cases. Streptococcus pneumoniae was present in 16% and Branhamella catarrhalis in 7% of cases. There was no association between specific viruses and bacteria observed in this study.

  1. A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice

    PubMed Central

    Milligan, Gregg N.; Sarathy, Vanessa V.; Infante, Ernesto; Li, Li; Campbell, Gerald A.; Beatty, P. Robert; Harris, Eva; Barrett, Alan D. T.; Bourne, Nigel

    2015-01-01

    Dengue is a mosquito-borne disease of global public health significance that is caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from a relatively mild self-limiting illness to a severe life-threatening disease. Infection with one serotype of DENV results in life-long homotypic immunity but only short term heterotypic protection. There are no licensed vaccines or antivirals for dengue due in part to difficulty in developing small animal models that mimic the systemic disease seen in humans. Consequently, an important advance was the description of models of DENV-2 infection in AG129 mice (deficient in interferon alpha/beta and gamma receptor signaling) that resemble human disease. However, the need for well characterized models of disease due to DENV-1, -3, and -4 still remains. Here we describe a new AG129 mouse model utilizing a non-mouse-adapted Thai human DENV-4 strain 703-4. Following intraperitoneal challenge, animals experience a rapidly progressive lethal infection without developing neurologic clinical signs of disease. High virus titers are seen in multiple visceral tissues including the liver, spleen and large intestine, and the infected animals develop vascular leakage and thrombocytopenia, hallmarks of human dengue. Taken together, our studies demonstrate that this model is an important addition to the field of dengue research particularly in understanding similarities and differences in the pathologic basis of the disease caused by different DENV serotypes and in determining comparative efficacy of putative vaccines and antivirals. PMID:25938762

  2. 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.

  3. 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.

  4. 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

  5. Dengue outbreak associated with multiple serotypes--Puerto Rico, 1998.

    PubMed

    1998-11-13

    Dengue is an acute viral disease caused by any of the four dengue virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4). The principal mosquito vector is Aedes aegypti, which has a worldwide distribution in tropical and many subtropical areas. All four virus serotypes produce a similar illness characterized by fever, headache, myalgias, arthralgias, rash, nausea and vomiting and induce life-long immunity that is specific to the infecting serotype. A small proportion of infected persons may develop the severe form of disease, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), but with early diagnosis and proper supportive management, fatality rates may be <1%. This report summarizes an epidemic of dengue in Puerto Rico in 1998 associated with multiple dengue serotypes.

  6. Syndromic surveillance: etiologic study of acute febrile illness in dengue suspicious cases with negative serology. Brazil, Federal District, 2008.

    PubMed

    Silva, Ailton Domicio da; Evangelista, Maria do Socorro Nantua

    2010-01-01

    With the aim of identifying the etiology of acute febrile illness in patients suspected of having dengue, yet with non reagent serum, a descriptive study was conducted with 144 people using secondary serum samples collected during convalescence. The study was conducted between January and May of 2008. All the exams were re-tested for dengue, which was confirmed in 11.8% (n = 17); the samples that remained negative for dengue (n = 127) were tested for rubella, with 3.9% (n = 5) positive results. Among those non reactive for rubella (n = 122), tests were made for leptospirosis and hantavirus. Positive tests for leptospirosis were 13.9% (n = 17) and none for hantavirus. Non reactive results (70.8%) were considered as Indefinite Febrile Illness (IFI). Low schooling was statistically associated with dengue, rubella and leptospirosis (p = 0.009), dyspnea was statistically associated with dengue and leptospirosis (p = 0.012), and exanthem/petechia with dengue and rubella (p = 0.001). Among those with leptospirosis, activities in empty or vacant lots showed statistical association with the disease (p = 0.013). Syndromic surveillance was shown to be an important tool in the etiologic identification of IFI in the Federal District of Brazil.

  7. Dengue virus: A global human threat: Review of literature

    PubMed Central

    Hasan, Shamimul; Jamdar, Sami Faisal; Alalowi, Munther; Al Ageel Al Beaiji, Sadun Mohammad

    2016-01-01

    Dengue is an acute viral illness caused by RNA virus of the family Flaviviridae and spread by Aedes mosquitoes. Presenting features may range from asymptomatic fever to dreaded complications such as hemorrhagic fever and shock. A cute-onset high fever, muscle and joint pain, myalgia, cutaneous rash, hemorrhagic episodes, and circulatory shock are the commonly seen symptoms. Oral manifestations are rare in dengue infection; however, some cases may have oral features as the only presenting manifestation. Early and accurate diagnosis is critical to reduce mortality. Although dengue virus infections are usually self-limiting, dengue infection has come up as a public health challenge in the tropical and subtropical nations. This article provide a detailed overview on dengue virus infections, varied clinical manifestations, diagnosis, differential diagnosis, and prevention and treatment. PMID:27011925

  8. Dengue virus: A global human threat: Review of literature.

    PubMed

    Hasan, Shamimul; Jamdar, Sami Faisal; Alalowi, Munther; Al Ageel Al Beaiji, Sadun Mohammad

    2016-01-01

    Dengue is an acute viral illness caused by RNA virus of the family Flaviviridae and spread by Aedes mosquitoes. Presenting features may range from asymptomatic fever to dreaded complications such as hemorrhagic fever and shock. A cute-onset high fever, muscle and joint pain, myalgia, cutaneous rash, hemorrhagic episodes, and circulatory shock are the commonly seen symptoms. Oral manifestations are rare in dengue infection; however, some cases may have oral features as the only presenting manifestation. Early and accurate diagnosis is critical to reduce mortality. Although dengue virus infections are usually self-limiting, dengue infection has come up as a public health challenge in the tropical and subtropical nations. This article provide a detailed overview on dengue virus infections, varied clinical manifestations, diagnosis, differential diagnosis, and prevention and treatment. PMID:27011925

  9. Type I Interferon Signals in Macrophages and Dendritic Cells Control Dengue Virus Infection: Implications for a New Mouse Model To Test Dengue Vaccines

    PubMed Central

    Toh, Ying-Xiu; Valdés, Iris; Cerny, Daniela; Heinrich, Julia; Hermida, Lisset; Marcos, Ernesto; Guillén, Gerardo; Kalinke, Ulrich; Shi, Pei-Yong; Fink, Katja

    2014-01-01

    ABSTRACT Dengue virus (DENV) infects an estimated 400 million people every year, causing prolonged morbidity and sometimes mortality. Development of an effective vaccine has been hampered by the lack of appropriate small animal models; mice are naturally not susceptible to DENV and only become infected if highly immunocompromised. Mouse models lacking both type I and type II interferon (IFN) receptors (AG129 mice) or the type I IFN receptor (IFNAR−/− mice) are susceptible to infection with mouse-adapted DENV strains but are severely impaired in mounting functional immune responses to the virus and thus are of limited use for study. Here we used conditional deletion of the type I IFN receptor (IFNAR) on individual immune cell subtypes to generate a minimally manipulated mouse model that is susceptible to DENV while retaining global immune competence. Mice lacking IFNAR expression on CD11c+ dendritic cells and LysM+ macrophages succumbed completely to DENV infection, while mice deficient in the receptor on either CD11c+ or LysM+ cells were susceptible to infection but often resolved viremia and recovered fully from infection. Conditional IFNAR mice responded with a swift and strong CD8+ T-cell response to viral infection, compared to a weak response in IFNAR−/− mice. Furthermore, mice lacking IFNAR on either CD11c+ or LysM+ cells were also sufficiently immunocompetent to raise a protective immune response to a candidate subunit vaccine against DENV-2. These data demonstrate that mice with conditional deficiencies in expression of the IFNAR represent improved models for the study of DENV immunology and screening of vaccine candidates. IMPORTANCE Dengue virus infects 400 million people every year worldwide, causing 100 million clinically apparent infections, which can be fatal if untreated. Despite many years of research, there are no effective vaccine and no antiviral treatment available for dengue. Development of vaccines has been hampered in particular by

  10. Dengue virus infection-enhancing and neutralizing antibody balance in children of the Philippines and Indonesia.

    PubMed

    Yamanaka, Atsushi; Tabuchi, Yuko; Mulyatno, Kris C; Susilowati, Helen; Hendrianto, Eryk; Soegijanto, Soegeng; Konishi, Eiji

    2012-11-01

    Dengue fever and dengue hemorrhagic fever are important diseases worldwide. Although antibody-dependent enhancement of infection has been proposed as a mechanism for increased disease severity, enhancing antibodies in endemic people have not been thoroughly investigated. Recently, we established a serological assay system to measure the balance of enhancing and neutralizing activities, which provides useful information for estimating in vivo antibody status. We measured the balance of these activities against four dengue virus (DENV) types in endemic populations, and analyzed the proportion of sera containing enhancing and neutralizing antibodies. Predominantly healthy Filipino children were used for analysis, although a population of Indonesian children was also investigated. In the Filipino population, the highest proportion of neutralizing activities was shown against DENV2, followed by DENV1. A greater proportion of sera exhibited enhancing rather than neutralizing antibodies against other virus types. Neutralizing activities were complement-dependent, while enhancing activities were complement-independent. The Indonesian population showed a similar dengue antibody status. Our results indicate that a relatively high proportion of endemic children possessed complement-independent enhancing antibodies against some DENV types.

  11. [Dengue fever and dengue hemorrhagic fever].

    PubMed

    Fonsmark, L; Poulsen, A; Heegaard, E D

    2000-09-18

    Dengue virus is transmitted by mosquitoes and causes dengue fever/dengue haemorrhagic fever throughout the tropical areas of the world. There is an increasing incidence of dengue infections. Because of increasing travel activity, infection among Danes travelling abroad as well as imported cases are expected to be seen more frequently. In this review we describe the clinical manifestations, diagnosis, pathogenesis, treatment and prevention of the disease.

  12. Epidemiological Risk Factors Associated with High Global Frequency of Inapparent Dengue Virus Infections

    PubMed Central

    Grange, Laura; Simon-Loriere, Etienne; Sakuntabhai, Anavaj; Gresh, Lionel; Paul, Richard; Harris, Eva

    2014-01-01

    Dengue is a major international public health concern, and the number of outbreaks has escalated greatly. Human migration and international trade and travel are constantly introducing new vectors and pathogens into novel geographic areas. Of particular interest is the extent to which dengue virus (DENV) infections are subclinical or inapparent. Not only may such infections contribute to the global spread of DENV by human migration, but also seroprevalence rates in naïve populations may be initially high despite minimal numbers of detectable clinical cases. As the probability of severe disease is increased in secondary infections, populations may thus be primed, with serious public health consequences following introduction of a new serotype. In addition, pre-existing immunity from inapparent infections may affect vaccine uptake, and the ratio of clinically apparent to inapparent infection could affect the interpretation of vaccine trials. We performed a literature search for inapparent DENV infections and provide an analytical review of their frequency and associated risk factors. Inapparent rates were highly variable, but “inapparent” was the major outcome of infection in all prospective studies. Differences in the epidemiological context and type of surveillance account for much of the variability in inapparent infection rates. However, one particular epidemiological pattern was shared by four longitudinal cohort studies: the rate of inapparent DENV infections was positively correlated with the incidence of disease the previous year, strongly supporting an important role for short-term heterotypic immunity in determining the outcome of infection. Primary and secondary infections were equally likely to be inapparent. Knowledge of the extent to which viruses from inapparent infections are transmissible to mosquitoes is urgently needed. Inapparent infections need to be considered for their impact on disease severity, transmission dynamics, and vaccine efficacy

  13. Dengue as a cause of fever during pregnancy: a report of two cases.

    PubMed

    Souza, Ariani Impieri; Ferreira, Ana Laura Carneiro Gomes; Arraes, Matheus Alencar; Moura, Bruno Marcelo; Braga, Maria Cynthia

    2016-01-01

    Dengue infection has not been routinely investigated among pregnant women and parturients with acute febrile syndrome in endemic settings. Here, we report two cases of dengue fever detected at the time of delivery in parturients enrolled in a cohort prospective study conducted in a hospital in Recife, Brazil. The parturients reported fever onset within seven days prior to delivery, and dengue infection was confirmed upon detection of viral ribonucleic acid (RNA) by using the reverse transcriptase-polymerase chain reaction. Dengue infection should be considered as a diagnostic possibility in cases of fever during pregnancy and labor, especially in endemic areas. PMID:27384840

  14. Dengue virus.

    PubMed

    Ross, Ted M

    2010-03-01

    Dengue is the most prevalent arthropod-borne virus affecting humans today. The virus group consists of 4 serotypes that manifest with similar symptoms. Dengue causes a spectrum of disease, ranging from a mild febrile illness to a life-threatening dengue hemorrhagic fever. Breeding sites for the mosquitoes that transmit dengue virus have proliferated, partly because of population growth and uncontrolled urbanization in tropical and subtropical countries. Successful vector control programs have also been eliminated, often because of lack of governmental funding. Dengue viruses have evolved rapidly as they have spread worldwide, and genotypes associated with increased virulence have spread across Asia and the Americas. This article describes the virology, epidemiology, clinical manifestations and outcomes, and treatments/vaccines associated with dengue infection.

  15. [Current status of dengue virus infections. Epidemiologic and pathogenetic aspects].

    PubMed

    Tolou, H; Baudon, D; Laroche, R

    1997-01-01

    The epidemiology of dengue fever is changing dramatically. The worldwide incidence is rising and clinical symptoms are worsening. Reports describing forms associated with hemorrhage or shock syndrome involving both children and adults are increasingly frequent in regions beyond Southeast Asia where the first cases were observed. Many mechanisms could be implicated in these changes including modifications of the virus, host, vector, or socioeconomic factors. Since no current model allows laboratory analysis of these mechanisms, observation of epidemics is still a major source of data. The findings of well conducted epidemiological studies allow not only assessment of morbidity and mortality in endemic areas and early detection of epidemic outbreaks but also evaluation of socioeconomic impact and effectiveness of control measures. Surveillance techniques must be chosen in function of prevailing local conditions. To ensure reliable results studies should be carried out in collaboration with an international network and a simple and accurate method of disease identification should be used.

  16. Dengue fever: a resurgent risk for the international traveler.

    PubMed

    Lange, W R; Beall, B; Denny, S C

    1992-03-01

    The incidence of dengue fever, an acute febrile illness transmitted by the Aedes aegypti mosquito, is on the rise. High fever, severe headache, skin rash and a variety of constitutional symptoms are hallmarks of classic dengue fever. Dengue hemorrhagic fever, a severe manifestation associated with secondary infection, most often occurs in children. Treatment of classic dengue fever is supportive, whereas urgent rehydration therapy is often required in more severe forms. Community-based and personal strategies for avoiding the mosquito vector represent the best methods of prevention, although vaccine development programs are under way.

  17. Dengue Fever: A Rare Cause Of Immune Thrombocytopenia.

    PubMed

    Ramírez-Fonseca, Tania; Segarra-Torres, Amaury; Jaume-Anselmi, Francisco; Ramírez-Rivera, José

    2015-01-01

    Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low platelet count and skin-mucosal bleeding. In adults it is usually idiopathic and may have a chronic onset, while in children it is usually acute following a viral illness. Dengue has been rarely reported as a cause of ITP. We report a case of a young adult woman that presented with acute ITP following a dengue virus infection.

  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

    2016-08-01

    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

  20. Clinical and laboratory features that differentiate dengue from other febrile illnesses in an endemic area--Puerto Rico, 2007-2008.

    PubMed

    Gregory, Christopher J; Santiago, Luis Manuel; Argüello, D Fermin; Hunsperger, Elizabeth; Tomashek, Kay M

    2010-05-01

    Dengue infection can be challenging to diagnose early in the course of infection before severe manifestations develop, but early diagnosis can improve patient outcomes and promote timely public health interventions. We developed age-based predictive models generated from 2 years of data from an enhanced dengue surveillance system in Puerto Rico. These models were internally validated and were able to differentiate dengue infection from other acute febrile illnesses with moderate accuracy. The accuracy of the models was greater than either the current World Health Organization case definition for dengue fever or a proposed modification to this definition, while requiring the collection of fewer data. In young children, thrombocytopenia and the absence of cough were associated with dengue infection; for adults, rash, leucopenia, and the absence of sore throat were associated with dengue infection; in all age groups, retro-orbital pain was associated with dengue infection.

  1. 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.

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

    PubMed

    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. 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

  4. HLA-A, -B, -C, and -DRB1 allele frequencies in Cuban individuals with antecedents of dengue 2 disease: advantages of the Cuban population for HLA studies of dengue virus infection.

    PubMed

    Sierra, Beatriz; Alegre, Roberto; Pérez, Ana B; García, Gissel; Sturn-Ramirez, Katharina; Obasanjo, Olugbenga; Aguirre, Eglys; Alvarez, Mayling; Rodriguez-Roche, Rosmari; Valdés, Luis; Kanki, Phyllis; Guzmán, María G

    2007-06-01

    Dengue virus infection has emerged as one of the most important arthropod-borne diseases. In some dengue-infected individual, the disease progresses to its severe, life-threatening form, dengue hemorrhagic fever (DHF). Host genetic factors may be relevant and predispose some individuals to the severe dengue disease. The unique history of dengue outbreaks in Cuba is extremely advantageous for genetic studies of dengue disease resistance or susceptibility. Consequently, samples collected from 120 healthy individuals that developed dengue fever (DF) and DHF during the 1997 dengue 2 outbreak in the Santiago de Cuba municipality were HLA genotyped using polymerase chain reaction-sequence-specific primers. Polymorphism at the human leukocyte antigen (HLA) class I loci was significantly associated with DHF disease susceptibility, but polymorphism in the HLA-DRB1 was associated with protection. Amino acid peptides present in the poly-protein of the dengue 2 Jamaica strain, which are able to bind to the HLA class I and class II allotypes associated with susceptibility to or protection against the dengue clinical disease, respectively, were predicted using the BIMAS and SYFPEITHI predictive algorithms of peptide/MHC interaction.

  5. A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus.

    PubMed

    Dejnirattisai, Wanwisa; Wongwiwat, Wiyada; Supasa, Sunpetchuda; Zhang, Xiaokang; Dai, Xinghong; Rouvinski, Alexander; Rouvinsky, Alexander; Jumnainsong, Amonrat; Edwards, Carolyn; Quyen, Nguyen Than Ha; Duangchinda, Thaneeya; Grimes, Jonathan M; Tsai, Wen-Yang; Lai, Chih-Yun; Wang, Wei-Kung; Malasit, Prida; Farrar, Jeremy; Simmons, Cameron P; Zhou, Z Hong; Rey, Felix A; Mongkolsapaya, Juthathip; Screaton, Gavin R

    2015-02-01

    Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized. PMID:25501631

  6. A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus.

    PubMed

    Dejnirattisai, Wanwisa; Wongwiwat, Wiyada; Supasa, Sunpetchuda; Zhang, Xiaokang; Dai, Xinghong; Rouvinski, Alexander; Rouvinsky, Alexander; Jumnainsong, Amonrat; Edwards, Carolyn; Quyen, Nguyen Than Ha; Duangchinda, Thaneeya; Grimes, Jonathan M; Tsai, Wen-Yang; Lai, Chih-Yun; Wang, Wei-Kung; Malasit, Prida; Farrar, Jeremy; Simmons, Cameron P; Zhou, Z Hong; Rey, Felix A; Mongkolsapaya, Juthathip; Screaton, Gavin R

    2015-02-01

    Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.

  7. Epidemic dengue hemorrhagic fever in rural Indonesia. I. Virological and epidemiological studies.

    PubMed

    Gubler, D J; Suharyono, W; Lubis, I; Eram, S; Sulianti Saroso, J

    1979-07-01

    Virological studies were carried out during an epidemic of dengue hemorrhagic fever in Central Java, Indonesia in 1976. Dengue virus was isolated from the acute sera of 45 of 69 patients (65%). The isolation rate was higher in primary than secondary cases. Dengue 3 was the predominant serotype being transmitted (27 isolates), but both dengue 1 (8 isolates) and dengue 4 (10 isolates) were also being transmitted. A composite picture of magnitude and duration of viremia showed that many patients were circulating over 10(8) MID50 per milliliter dengue 3 virus for the first 3 days of illness and that viremia persisted for 5-6 days in some persons. If all shock cases were considered, there was no relationship between dengue serotype and severity of disease. All three confirmed fatal cases, however, were associated with dengue type 3 infections.

  8. 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

  9. 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

  10. DC-SIGN (CD209) Carbohydrate Recognition Domain Is Not Polymorphic in Dengue Virus-Infected Indonesian Patients.

    PubMed

    Wibawa, Tri; Wijayanti, Nastiti; Arguni, Eggi; Laksono, Ida Safitri

    2015-06-01

    Dengue virus (DENV) infection is a significant burden in Indonesia and other tropical countries. DENV infection has a wide spectrum of clinical manifestations, i.e. asymptomatic, dengue fever, dengue hemorrhagic fever and dengue shock syndrome. The variety of clinical manifestations may be due to the diversity of genetic constitution of the host. The C-type lectin DC-SIGN (CD209) has been identified as the major dengue receptor on human dendritic cells. There are at least five polymorphisms in exon 5 and 6 of the DC-SIGN encoded gene which have been identified and recorded in dbSNP. The aim of this work is to measure the frequency of these polymorphisms among asymptomatic and hospitalized DENV-infected patients. We enrolled 23 hospitalized and 73 asymptomatic DENV-infected patients. Among the subjects, we performed PCR amplification and DNA direct seqencing for 23 hospitalized DENV-infected patients and 24 asymptomatic DENV-infected patients. The result showed that there were no polymorphic nucleotides in the CD209 encoded gene among the patients. PMID:26161028

  11. DC-SIGN (CD209) Carbohydrate Recognition Domain Is Not Polymorphic in Dengue Virus-Infected Indonesian Patients.

    PubMed

    Wibawa, Tri; Wijayanti, Nastiti; Arguni, Eggi; Laksono, Ida Safitri

    2015-06-01

    Dengue virus (DENV) infection is a significant burden in Indonesia and other tropical countries. DENV infection has a wide spectrum of clinical manifestations, i.e. asymptomatic, dengue fever, dengue hemorrhagic fever and dengue shock syndrome. The variety of clinical manifestations may be due to the diversity of genetic constitution of the host. The C-type lectin DC-SIGN (CD209) has been identified as the major dengue receptor on human dendritic cells. There are at least five polymorphisms in exon 5 and 6 of the DC-SIGN encoded gene which have been identified and recorded in dbSNP. The aim of this work is to measure the frequency of these polymorphisms among asymptomatic and hospitalized DENV-infected patients. We enrolled 23 hospitalized and 73 asymptomatic DENV-infected patients. Among the subjects, we performed PCR amplification and DNA direct seqencing for 23 hospitalized DENV-infected patients and 24 asymptomatic DENV-infected patients. The result showed that there were no polymorphic nucleotides in the CD209 encoded gene among the patients.

  12. 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.

  13. Utility of a Dengue-Derived Monoclonal Antibody to Enhance Zika Infection In Vitro

    PubMed Central

    Charles, Anu Susan; Christofferson, Rebecca C.

    2016-01-01

    Introduction: Zika virus (ZIKV) has emerged in dengue (DENV) endemic areas, where these two related flaviviruses continue to co-circulate. DENV is a complex of four serotypes and infections can progress to severe disease. It is thought that this is mediated by antibody dependent enhancement (ADE) whereby antibodies from a primary DENV infection are incapable of neutralizing heterologous DENV infections with another serotype. ADE has been demonstrated among other members of the Flavivirus group. Methods: We utilize an in vitro ADE assay developed for DENV to determine whether ZIKV is enhanced by a commonly available DENV serotype 2-derived monoclonal antibody (4G2). Results: We show that ZIKV infection in vitro is enhanced in the presence of the 4G2 mAb. Discussion: Our results demonstrate that ADE between ZIKV and DENV is possible and that the 4G2 antibody is a useful tool for the effects of pre-existing anti-DENV antibodies during ZIKV infections.

  14. 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.

  15. Clinical factors associated with mortality in dengue infection at a tertiary care center.

    PubMed

    Almas, Aysha; Parkash, Om; Akhter, Jaweed

    2010-03-01

    We conducted a cross-sectional study to investigate the clinical factors associated with mortality in patients with dengue viral infection at a tertiary care center over a 3 year period. Six hundred ninety-nine patients with a clinical diagnosis of dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) during the study period were included in the study. Data were collected with a predesigned form comprised of demographics, duration of fever, associated symptoms, diagnosis of DF, DHF and DSS, and laboratory parameters [complete blood count, coagulation tests, creatinine, serum glutamic pyruvic transaminase (SGPT)]; dengue IgM was checked in all patients by ELISA. Outcomes (survival/mortality) and complications were recorded. Mortality was the primary outcome measure. DF constituted 86.4% (604), DHF constituted 11.6% (81) and DSS constituted 2% (14) of patients. The mortality rate was 2.7% (19). The mean white blood cell count in those who died was 13.3, in those who survived was 5.3, the difference was significant (p = 0.02). The mean BUN in those who died was 33.2, those who survived was 13.8, (p = 0.007). The mean bicarbonate level in those who died was 17.1, those who survived was 18.5 (p < 0.001). Mean activated partial thromboplastin time in those who died was 56.8, those who survived was 36.8 (p = 0.01). The mean SGPT in those who died was 802, those who survived was 176 (p = 0.01). Those who died were significantly (p < 0.001) more likely to have severe hepatitis (63%) than those who survived (13.8%). On multivariate logistic regression analysis, having an SGPT >300 mg/dl, bleeding, an altered mental status and shock at presentation were all significantly associated with mortality in patients with dengue virus infection (p = 0.008, p < 0.001, p < 0.001, p < 0.001, respectively).

  16. Characterization of a dengue patient cohort in Recife, Brazil.

    PubMed

    Cordeiro, Marli Tenório; Silva, Ana Maria; Brito, Carlos A A; Nascimento, Eduardo J M; Magalhães, Maria Cecilia F; Guimarães, Georgia F; Lucena-Silva, Norma; de Carvalho, Eduardo M Freese; Marques, Ernesto T A

    2007-12-01

    From 2004 to 2006, 658 patients with suspected dengue virus infections were enrolled in a clinical dengue cohort established in Recife, Pernambuco, located at the northeastern region of Brazil. A total of 2,364 blood samples were collected, and serum, plasma, and cells were cryopreserved. Among the suspected cases, 354 (54%) were confirmed as acute DENV-3 infection based on reverse transcription-polymerase chain reaction, virus isolation, and ELISA-IgM. According to WHO criteria, 29.4% of the positive acute cases were classified as dengue fever (DF) and 8.2% of the cases as dengue hemorrhagic fever (DHF), grade 1 or 2. The DHF cases represent 100% of those confirmed in Recife during the period of the study. The dengue cases that did not fulfill the definition of either DHF or DF were classified as DF complicated and accounted for 44.0% of the cases. All the acute cases were classified as either primary or secondary acute dengue virus infections. Secondary infection was predominant in patients with DF; however, there was no predominance of either primary or secondary infections in patients with DHF.

  17. 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.

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

    PubMed

    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

  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. Dengue fever

    MedlinePlus

    ... 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 ...

  2. Dengue virus infections and maternal antibody decay in a prospective birth cohort study of Vietnamese infants.

    PubMed

    Chau, Tran Nguyen Bich; Hieu, Nguyen Trong; Anders, Katherine L; Wolbers, Marcel; Lien, Le Bich; Hieu, Lu Thi Minh; Hien, Tran Tinh; Hung, Nguyen Thanh; Farrar, Jeremy; Whitehead, Stephen; Simmons, Cameron P

    2009-12-15

    Dengue hemorrhagic fever can occur in primary dengue virus (DENV) infection of infants. The decay of maternally derived DENV immunoglobulin (Ig) G and the incidence of DENV infection were determined in a prospectively studied cohort of 1244 Vietnamese infants. Higher concentrations of total IgG and DENV-reactive IgG were found in cord plasma relative to maternal plasma. Maternally derived DENV-neutralizing and E protein-reactive IgG titers declined to below measurable levels in >90% of infants by 6 months of age. In contrast, IgG reactive with whole DENV virions persisted until 12 months of age in 20% of infants. Serological surveillance identified 10 infants with asymptomatic DENV infection for an incidence of 1.7 cases per 100 person-years. DENV-neutralizing antibodies remained measurable for > or = 1 year after infection. These results suggest that whereas DENV infection in infants is frequently subclinical, there is a window between 4 and 12 months of age where virion-binding but nonneutralizing IgG could facilitate antibody-dependent enhancement.

  3. Virologic and serologic surveillance for dengue fever in Jeddah, Saudi Arabia, 1994-1999.

    PubMed

    Fakeeh, M; Zaki, A M

    2001-12-01

    Dengue fever infection was first documented in Jeddah, Saudi Arabia, by virus isolation of dengue type 2 virus in 1994 at the virology laboratory of Dr. Soliman Fakeeh Hospital. Dengue virus surveillance was established after that time. Blood samples were collected from 985 patients (710 male patients and 275 female patients) with suspected cases of dengue from February 1994 to December 1999. Dengue virus isolates were obtained in 207 patients (21%; 162 male patients and 45 female patients). Dengue type 2 was the predominant serotype (138 of 207 isolates, 66.7%), followed by dengue type 1 with (56 of 207 isolates, 27%) and dengue type 3 (13 of 207 isolates, 6.3%). The largest number of isolates (186 of 207 isolates, 90%) was in 1994, a year during which there was a dengue epidemic. In the next 5 years, 1995-1999, only 21 isolates (10%) were isolated. Immunoglobulin M capture enzyme-linked immunosorbent assay was positive in 160 acute samples; 52 of them were from virus culture-positive cases and 108 (11%) from culture-negative cases. The total number of cases diagnosed by both methods was 315 (32%). The prevalence of dengue immunoglobulin G antibodies, as assessed on the basis of immunofluorescent assay, hemagglutination inhibition titers > or = 1/20, or both, in the acute samples was 314 (32%) of 985, indicating past Flavivirus infection. Two patients died, one man with dengue hemorrhagic fever and one woman with dengue shock syndrome. Both fatal dengue cases were due to infection with type 2 virus. All other cases were simple dengue fever. To our knowledge, this is the first report confirming the circulation of 3 dengue serotypes in Jeddah.

  4. 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

  5. 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.

  6. 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.

  7. Role of CC chemokine receptor 1 and two of its ligands in human dengue infection. Three approaches under the Cuban situation.

    PubMed

    Sierra, Beatriz; Perez, Ana B; Garcia, Gissel; Aguirre, Eglys; Alvarez, Mayling; Gonzalez, Daniel; Guzman, Maria G

    2014-01-01

    Any of the four dengue serotypes can cause a severe disease, partly due to systemic inflammation orchestrated by mediators like cytokines and chemokines. We addressed the role of CCR1 and its ligands CCL3/MIP-1α and CCL5/RANTES in dengue infection using three different approaches: an ex vivo model exploring memory immune response in subjects with a well characterized dengue immune background, an in vivo study in patients with primary or secondary dengue infection, and an approach in fatal dengue. CCR1 and CCL3/MIP-1α gene expression showed differences after homotypic and heterotypic challenge according to dengue immune background of subjects, in correspondence with previous observations in Cuban dengue outbreaks. CCL5/RANTES gene expression was higher after homotypic challenge. CCR1 and CCL3/MIP-1α gene expression was higher in patients with secondary infection during critical days of the dengue disease, while the increase in RANTES expression started earlier than the observed for CCR1 and CCL3/MIP-1α. CCR1 and CCL3/MIP-1α gene expression was as high in brain as in spleen tissue from necropsy. Our results confirm the strong influence of previous immunity in subsequent dengue infections, and confer a possible pathogenic role to CCR1 and CCL3/MIP-1α in dengue disease and a possible protective role for CCL5/RANTES, probably through CCR5 interaction.

  8. [Dengue vaccines].

    PubMed

    Morita, Kouichi

    2008-10-01

    Dengue is the most important mosquito borne virus infection in the tropics. Based on the effects of global warming, it is expected that dengue epidemic areas will further expand in the next decades unless effective and affordable vaccines are made available soon. At the moment, several vaccine developers have utilized live-attenuated live tetravalent vaccines and two of them have already completed phase two trials. However, the risk of antibody-dependent enhancement infection is not well elucidated and thus further and careful evaluation of the safety on proposed candidate vaccines are essential. At the moment, Bill and Melinda Gates Foundation strongly support the vaccine development through the Pediatric Dengue Vaccine Initiative.

  9. When to consider acute HIV infection in the differential diagnosis.

    PubMed

    Grimes, Richard M; Hardwicke, Robin L; Grimes, Deanna E; DeGarmo, D Sean

    2016-01-16

    Patients presenting with fever, pharyngitis, and lymphadenopathy are likely to have mononucleosis; however, patients with acute HIV infection may present with similar symptoms. Acute HIV infection should be considered as a differential diagnosis if test results for mononucleosis are negative. This article describes when to order HIV testing and discusses the importance of early intervention for acute HIV infection. PMID:26678418

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

    PubMed Central

    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.

    2014-01-01

    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. PMID:24847073

  11. Selective Susceptibility of Human Skin Antigen Presenting Cells to Productive Dengue Virus Infection

    PubMed Central

    Cerny, Daniela; Haniffa, Muzlifah; Shin, Amanda; Bigliardi, Paul; Tan, Bien Keem; Lee, Bernett; Poidinger, Michael; Tan, Ern Yu; Ginhoux, Florent; Fink, Katja

    2014-01-01

    Dengue is a growing global concern with 390 million people infected each year. Dengue virus (DENV) is transmitted by mosquitoes, thus host cells in the skin are the first point of contact with the virus. Human skin contains several populations of antigen-presenting cells which could drive the immune response to DENV in vivo: epidermal Langerhans cells (LCs), three populations of dermal dendritic cells (DCs), and macrophages. Using samples of normal human skin we detected productive infection of CD14+ and CD1c+ DCs, LCs and dermal macrophages, which was independent of DC-SIGN expression. LCs produced the highest viral titers and were less sensitive to IFN-β. Nanostring gene expression data showed significant up-regulation of IFN-β, STAT-1 and CCL5 upon viral exposure in susceptible DC populations. In mice infected intra-dermally with DENV we detected parallel populations of infected DCs originating from the dermis and migrating to the skin-draining lymph nodes. Therefore dermal DCs may simultaneously facilitate systemic spread of DENV and initiate the adaptive anti-viral immune response. PMID:25474532

  12. Randomized comparison of oxygen mask treatment vs. nasal continuous positive airway pressure in dengue shock syndrome with acute respiratory failure.

    PubMed

    Cam, B V; Tuan, D T; Fonsmark, L; Poulsen, A; Tien, N M; Tuan, H M; Heegaard, E D

    2002-12-01

    Dengue hemorrhagic fever (DHF) is caused by dengue virus. Patients with DHF grade 3-4, termed Dengue Shock Syndrome (DSS), may develop acute respiratory failure after initial fluid resuscitation. Previously, these patients were treated with oxygen on a nasal cannula, or if necessary with tracheal intubation and mechanical ventilation. In the present prospective randomized study, we compared the effectiveness of oxygen treatment administered by a face mask vs. nasal continuous positive airway pressure (NCPAP). Morbidity, mortality, and supportive treatment was evaluated. Thirty-seven patients with DSS complicated by respiratory failure were enrolled. On admission and after 30 min of treatment, clinical and paraclinical data were obtained. Chest X-ray revealed pleural effusion in 92 per cent and showed interstitial oedema in 33 per cent. After 30 min of treatment the respiratory rate decreased significantly in the NCPAP group (p < 0.05), while SaO2 and PaO2 increased in both groups (p < 0.01). However, subsequently a significant difference of unresponsiveness to treatment between the oxygen mask group and the NCPAP group (13/19 vs. 4/18,p < 0.01) was noted. Complications of NCPAP or oxygen mask treatment were not documented. We conclude that NCPAP is useful in improving the management of acute respiratory failure in children with DHF/DSS in dengue-endemic areas.

  13. 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.

  14. 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

    2015-08-01

    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. PMID:26195744

  15. Single nucleotide polymorphisms in immune system genes and their association with clinical symptoms persistence in dengue-infected persons.

    PubMed

    Dettogni, Raquel Spinassé; Tristão-Sá, Ricardo; Dos Santos, Marcelo; da Silva, Franciane Figueiredo; Louro, Iúri Drumond

    2015-10-01

    This study was undertaken to determine the prevalence of dengue clinical symptom persistence during 60days of disease follow up, in patients of Espírito Santo state (ES)-Brazil and to evaluate the relation of single nucleotide polymorphisms (SNPs) in FcγRIIa, CD209, VDR, TNF-α, IL-4, IL-6 and IFN-γ genes with symptom persistence. During 2012-2013, 96 blood samples from individuals diagnosed with symptomatic dengue were collected. Clinical symptom persistence in 60days of follow-up was assessed by a clinical and epidemiological questionnaire filled in 4 interviews. SNP genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In two months of monitoring the dengue infection, we observed that symptoms persisted in 38.5% (37/96) of dengue patients at the end of the first month (D30) and in 11.5% (11/96) of dengue patients at the end of the second month (D60). Our results show an association between FcγRIIa, TNF-α and IL-6 gene SNPs and symptom persistence and an association trend with CD209, IL-4 and IFN-γ gene SNPs. Our findings may increase the knowledge on the pathophysiological mechanisms of persistent symptoms of infection with the dengue virus (DENV) and thus help the clinical management of patients.

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

    PubMed Central

    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.

    2015-01-01

    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. PMID:26491875

  17. 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.

  18. Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India--Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity.

    PubMed

    Singla, Mohit; Kar, Meenakshi; Sethi, Tavpritesh; Kabra, Sushil K; Lodha, Rakesh; Chandele, Anmol; Medigeshi, Guruprasad R

    2016-03-01

    Dengue virus, a mosquito-borne flavivirus, is a causative agent for dengue infection, which manifests with symptoms ranging from mild fever to fatal dengue shock syndrome. The presence of four serotypes, against which immune cross-protection is short-lived and serotype cross-reactive antibodies that might enhance infection, pose a challenge to further investigate the role of virus and immune response in pathogenesis. We evaluated the viral and immunological factors that correlate with severe dengue disease in a cohort of pediatric dengue patients in New Delhi. Severe dengue disease was observed in both primary and secondary infections. Viral load had no association with disease severity but high viral load correlated with prolonged thrombocytopenia and delayed recovery. Severe dengue cases had low Th1 cytokines and a concurrent increase in the inflammatory mediators such as IL-6, IL-8 and IL-10. A transient increase in CD14+CD16+ intermediate monocytes was observed early in infection. Sorting of monocytes from dengue patient peripheral blood mononuclear cells revealed that it is the CD14+ cells, but not the CD16+ or the T or B cells, that were infected with dengue virus and were major producers of IL-10. Using the Boruta algorithm, reduced interferon-α levels and enhanced aforementioned pro-inflammatory cytokines were identified as some of the distinctive markers of severe dengue. Furthermore, the reduction in the levels of IL-8 and IL-10 were identified as the most significant markers of recovery from severe disease. Our results provide further insights into the immune response of children to primary and secondary dengue infection and help us to understand the complex interplay between the intrinsic factors in dengue pathogenesis.

  19. Epidemiology and control of dengue virus infections in Thai villages in 1987.

    PubMed

    Eamchan, P; Nisalak, A; Foy, H M; Chareonsook, O A

    1989-07-01

    A severe epidemic of dengue hemorrhagic fever (DHF) in Nakhon Ratchasima, Thailand in August of 1987 prompted a field investigation. DHF rates of 0.4-6.5 cases per 1,000 residents in subdistricts and 2-15 cases per 1,000 residents in 10 villages investigated were reported. Epidemics peaked in neighboring villages at different times; in June and July, and in August before the rainy season began late in the month. In 4 primary schools representing 6 villages, sera from groups of randomly selected children were tested for dengue IgM with the antibody capture ELISA test. Rates of recent dengue infection were 10-65% in the schools and correlated closely with reported rates of DHF. In an effort to control vectors, malathion fog and temephos (1% abate sand granules) were applied. Villagers were educated in prevention and were urged to cover water receptacles. The percentage of houses with larvae dropped from 67 to 20, the percentage of containers with larvae decreased from 30 to 5, and the number of containers with larvae per 100 households decreased from 221 to 33. This was a serious epidemic in which conventional control measures were only moderately effective.

  20. [Unexpected Diseases in Two Patients with False-Positive Dengue Immunoglobulin M Antibody Test Results].

    PubMed

    Matono, Takashi; Kutsuna, Satoshi; Kato, Yasuyuki; Takeshita, Nozomi; Hayakawa, Kayoko; Kanagawa, Shuzo; Ohmagari, Norio

    2016-03-01

    In 2014, an outbreak of 162 domestic dengue fever infections occurred in Tokyo, Japan; the first outbreak of its kind in 70 years. Nineteen of these cases were confirmed in our center. Advancements in diagnostic methods have enabled an earlier diagnosis of dengue fever; however, unfamiliarity with the clinical course and characteristics of diagnostic tests for dengue fever can lead to misdiagnosis. We herein describe 2 cases of Japanese patients with false-positive dengue immunoglobulin M antibody test results, who were finally diagnosed as having dermatomyositis and acute hepatitis A infection, respectively. PMID:27197439

  1. Outbreak of febrile illness due to dengue virus type 3 in Calcutta during 1983.

    PubMed

    Mukherjee, K K; Chakravarti, S K; Dey, P N; Dey, S; Chakraborty, M S

    1987-01-01

    An epidemic of dengue fever broke out in Calcutta between July and August 1983. Persons of all age groups were affected with a preponderance of young adults. Haemorrhagic manifestations and shock were not observed. Virus was isolated from 4 acute phase sera and identified as dengue type 3 (DEN-3), the first isolation of DEN-3 virus in Calcutta. Serotesting with 9 paired blood samples established dengue infection in 7 and a flavivirus group reaction in 2. Examination of 36 single sera revealed presumptive dengue infection in 15 and a flavivirus group reaction in 17, while the remaining 4 were negative to all flavivirus antigens.

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

    PubMed Central

    Clapham, Hannah E; Dorigatti, Ilaria; Simmons, Cameron P; Ferguson, Neil M

    2016-01-01

    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. PMID:27213681

  3. 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

  4. Peritoneal infection in acute intermittent peritoneal dialysis.

    PubMed

    Sharma, Raj Kumar; Kumar, Jitendra; Gupta, Amit; Gulati, Sanjeev

    2003-11-01

    A prospective study was done to evaluate the incidence and microbiological trend of peritoneal infection in patients undergoing acute intermittent peritoneal dialysis (PD). Complete sterile procedure was ensured and at the completion of the procedure PD fluid was sent for bacteriological culture, sensitivity, and total and differential cell count. During the period September 2000 to February 2001 a total of 100 patients were evaluated. Male female ratio was 72:28. Mean age was 43.17 +/- 17.2 years. In 26 patients cyclers were used. Bacterial culture was positive in total of 30 cases (30%). Gram positive, Gram negative and mixed infection was found in 10%, 15%, and 5% respectively. Number of exchanges (31.61 +/- 7.7 vs. 31.3 +/- 6, p = 0.8) were similar and number of repositioning was significantly more in the infected group (23.3% vs. 11.4%, p < 0.01). Total cell count was significantly higher in infected group (274.3 +/- 502 vs. 31.25 +/- 79.34, p < 0.01). Among Gram +ve organisms Staphylococcus was found in 7, Enterococcus faecalis in 4 and Coryne bacterium sps. in 2 cases. Among Gram -ve organisms, E. coli was found in 4, Enterobacter in 3, Klebsiella 1, Pseudomonas 1, Acinetobacter arinatus 5, Acinetobacter baumani 3, and Citrobacter freundii 3. Mixed flora comprised of Enterococcus faecalis 3, Enterobacter 1, Staphlococcus 1, E. coli 3, Citrobacter 1, Acinobacter baumani 1. Although with the cyclers using collapsible bags, staphylococcus was not isolated, the total incidence of infection (11/26 cases) was not decreased with the use of cyclers. We conclude that in acute intermittent peritoneal dialysis the incidence of bacterial infection is 30% with preponderance of Gram -ve over Gram +ve organisms and organism of fecal origin being commoner than those of skin origin. Use of cycler-assisted over manual PD do not improve the incidence of infection. Repositioning of the stiff catheter significantly increases the incidence of infection.

  5. Differential Protein Modulation in Midguts of Aedes aegypti Infected with Chikungunya and Dengue 2 Viruses

    PubMed Central

    Tchankouo-Nguetcheu, Stéphane; Khun, Huot; Pincet, Laurence; Roux, Pascal; Bahut, Muriel; Huerre, Michel; Guette, Catherine; Choumet, Valérie

    2010-01-01

    Background Arthropod borne virus infections cause several emerging and resurgent infectious diseases. Among the diseases caused by arboviruses, dengue and chikungunya are responsible for a high rate of severe human diseases worldwide. The midgut of mosquitoes is the first barrier for pathogen transmission and is a target organ where arboviruses must replicate prior to infecting other organs. A proteomic approach was undertaken to characterize the key virus/vector interactions and host protein modifications that happen in the midgut for viral transmission to eventually take place. Methodology and Principal Findings Using a proteomics differential approach with two-Dimensional Differential in-Gel Electrophoresis (2D-DIGE), we defined the protein modulations in the midgut of Aedes aegypti that were triggered seven days after an oral infection (7 DPI) with dengue 2 (DENV-2) and chikungunya (CHIKV) viruses. Gel profile comparisons showed that the level of 18 proteins was modulated by DENV-2 only and 12 proteins were modulated by CHIKV only. Twenty proteins were regulated by both viruses in either similar or different ways. Both viruses caused an increase of proteins involved in the generation of reactive oxygen species, energy production, and carbohydrate and lipid metabolism. Midgut infection by DENV-2 and CHIKV triggered an antioxidant response. CHIKV infection produced an increase of proteins involved in detoxification. Conclusion/Significance Our study constitutes the first analysis of the protein response of Aedes aegypti's midgut infected with viruses belonging to different families. It shows that the differentially regulated proteins in response to viral infection include structural, redox, regulatory proteins, and enzymes for several metabolic pathways. Some of these proteins like antioxidant are probably involved in cell protection. On the other hand, we propose that the modulation of other proteins like transferrin, hsp60 and alpha glucosidase, may favour

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

    PubMed Central

    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; Van Vinh Chau, Nguyen; Wills, Bridget; Simmons, Cameron P.

    2015-01-01

    Dengue is the most common arboviral infection of humans and a public health burden in over 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 importantly did reduce the prevalence of mosquitoes with infectious saliva. A mathematical model of DENV transmission incorporating the dynamics of viral infection within 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 66–75%. Our results suggest that establishment of wMelPop-infected A. aegypti at high frequency in a dengue endemic setting would result in 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. PMID:25787763

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

    PubMed

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

    2013-11-12

    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.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26378567

  9. Inflammatory mediators in dengue virus infection in children: interleukin-6 and its relation to C-reactive protein and secretory phospholipase A2.

    PubMed

    Juffrie, M; Meer, G M; Hack, C E; Haasnoot, K; Sutaryo; Veerman, A J; Thijs, L G

    2001-07-01

    To assess the potential role of interleukin-6 (IL-6) in the pathogenesis of dengue virus infection, levels of this cytokine were measured in children with dengue virus infection on admission to the hospital. As presumed surrogate markers of IL-6, C-reactive protein (CRP) and secretory phospholipase A2 (sPLA2) were measured. Three groups were studied: 33 apparently healthy children as negative controls, 11 children with bacterial infections as positive controls, and 186 children with serologically documented dengue virus infection. One-hundred and fifteen patients had dengue fever (DF) and 71 had dengue hemorrhagic fever (DHF). Compared with healthy controls, dengue shock syndrome (DSS) patients had significantly higher levels of IL-6 on admission (P < 0.05), comparable with those in positive controls. Dengue patients with shock had significantly higher levels of IL-6 than normotensive patients (P < 0.001) and higher levels of IL-6 were associated with a higher incidence of ascites. C-reactive protein concentrations in dengue patients and in healthy children were not different, but lower than in children with bacterial infections (P = 0.008). Secretory phospholipase A2 levels were higher in dengue patients than in apparently healthy children (P < or = 0.05) and similar to those in children with bacterial infection. Dengue shock syndrome patients had significantly higher sPLA2 concentrations than normotensive patients (P = 0.02). These data indicate that IL-6 and sPLA2 may have a pathogenetic role only in the most severe forms of dengue virus infection.

  10. Elucidating the role of T cells in protection against and pathogenesis of dengue virus infections

    PubMed Central

    Mathew, Anuja; Townsley, Elizabeth; Ennis, Francis A

    2014-01-01

    Dengue viruses (DENV) cause significantly more human disease than any other arbovirus, with hundreds of thousands of cases leading to severe disease in thousands annually. Antibodies and T cells induced by primary infection with DENV have the potential for both positive (protective) and negative (pathological) effects during subsequent DENV infections. In this review, we summarize studies that have examined T-cell responses in humans following natural infection and vaccination. We discuss studies that support a role for T cells in protection against and those that support a role for the involvement of T cells in the pathogenesis of severe disease. The mechanisms that lead to severe disease are complex, and T-cell responses are an important component that needs to be further evaluated for the development of safe and efficacious DENV vaccines. PMID:24762312

  11. Viral respiratory tract infections among patients with acute undifferentiated fever in Vietnam.

    PubMed

    Phuong, Hoang Lan; Nga, Tran T T; van Doornum, Gerard J; Groen, Jan; Binh, Tran Q; Giao, Phan T; Hung, Le Q; Nams, Nguyen V; Kager, P A; de Vries, Peter J

    2010-09-01

    To investigate the proportion of viral respiratory tract infections among acute undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve primary health facilities and a clinic for malaria control program. Serum was collected on first presentation (t0) and after 3 weeks (t3) for serology. After exclusion of acute dengue infection, acute and convalescent serum samples from 606 patients were using enzyme-linked immunoassays to detect IgA, as well as IgM and IgG antibodies against common respiratory viruses. Paired sera showed the following infections: human parainfluenza virus (HPIV, 4.7%), influenza B virus (FLUBV, 2.2%), influenza A virus (FLUAV, 1.9%) and human respiratory syncytial virus (HRSV, 0.6%). There was no association between type of infection and age, sex or seasonality; some inter-annual differences were observed for influenza. Antibody prevalence, indicative of previous infections, was relatively low: HPV, 56.8%, FLUBV, 12.1%; FLUAV, 5.9% and HRSV, 6.8%.

  12. 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

  13. 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

  14. Antibody-dependent enhancement of dengue virus infection is inhibited by SA-17, a doxorubicin derivative.

    PubMed

    Ayala-Nuñez, Nilda V; Jarupathirun, Patsaporn; Kaptein, Suzanne J F; Neyts, Johan; Smit, Jolanda M

    2013-10-01

    Antibody-dependent enhancement (ADE) is thought to play a critical role in the exacerbation of dengue virus (DENV)-induced disease during a heterologous re-infection. Despite ADE's clinical impact, only a few antiviral compounds have been assessed for their anti-ADE activity. We reported earlier that SA-17, a doxorubicin derivative, efficiently inhibits the in vitro infection of DENV and yellow fever virus. Here we explored SA-17's mechanism of inhibition and investigated if the compound is active against ADE of DENV infection. Since enhanced infectivity stimulated by antibodies has been observed with standard and immature DENV, both types of virions were included in the study. We observed that SA-17 (i) inhibits DENV infection by preventing binding/entry to the cell and (ii) interferes with antibody-mediated infection of both standard and immature DENV2. SA-17 markedly reduced the infectivity of DENV2 in ADE conditions, with IC50s ranging from 0.26 to 2.89μM. The compound exerted its activity when added before, during, and after antibody-opsonization of standard and immature virus. Thus, molecules with the characteristics of SA-17 may be attractive antiviral agents since they can be used both to block DENV2 entry during primary and secondary infection and to inhibit ADE of standard and immature virus. PMID:23994499

  15. Incidence and risk factors of probable dengue virus infection among Dutch travellers to Asia.

    PubMed

    Cobelens, Frank G J; Groen, Jan; Osterhaus, Albert D M E; Leentvaar-Kuipers, Anne; Wertheim-van Dillen, Pauline M E; Kager, Piet A

    2002-04-01

    We studied the incidence of dengue virus (DEN) infections in a cohort of Dutch short-term travellers to endemic areas in Asia during 1991-92. Sera were collected before and after travel. All post-travel sera were tested for DEN immunoglobulin M (IgM) [IgM capture (MAC)-enzyme-linked immunosorbent assay (ELISA)] and IgG (indirect ELISA). Probable DEN infection was defined as IgM seroconversion or a fourfold rise in IgG ratio in the absence of cross-reaction with antibody to Japanese encephalitis virus (JEV). Infections were considered clinically apparent in case of febrile illness (> 24 H) with headache, myalgia, arthralgia or rash. Probable DEN infection was found in 13 of 447 travellers (incidence rate 30/1000 person-months, 95% CI 17.4-51.6). One infection was considered secondary; no haemorrhagic fever occurred. The clinical-to-subclinical infection rate was 1 : 3.3. The risk of infection showed marked seasonal variation. DEN infections are frequent in travellers to endemic areas in Asia; most remain subclinical.

  16. Genetic characterization of dengue virus serotypes causing concurrent infection in an outbreak in Ernakulam, Kerala, South India.

    PubMed

    Anoop, M; Issac, Aneesh; Mathew, Thomas; Philip, Sairu; Kareem, Nabeel Abdul; Unnikrishnan, R; Sreekumar, E

    2010-08-01

    Dengue fever, a mosquito-borne viral infection, causes significant morbidity and has become endemic in the Indian subcontinent. Virus strains currently circulating in many parts of the country are not well studied at the molecular level. In the present study, genetic characterization of virus strains from a dengue outbreak that occurred in and around a tertiary care hospital in Ernakulam, Kerala in the year 2008 has been reported. By reverse transcription polymerase chain reaction (RT-PCR), 37 out of 75 (49.3%) clinically suspected cases were positive for dengue viral RNA. Among these, 21 (56.8%) samples showed concurrent infection with multiple serotypes of the virus. Majority of the combined infections were caused by dengue serotype 2 and 3. Co-infections with type 1 and 2 in two patients, and type 1, 2 and 3 in one patient were also observed. The core-pre-Membrane (CprM) junction nucleotide sequencing and phylogenetic analysis revealed that the type 1 strains were related to the viral strains reported from Delhi-2001 and Gwalior-2002 dengue outbreaks, while the type 2 strains were related to the strains from Gwalior-2001 epidemic. Sequences of type 3 strains did not show clear relation to any of the previous Indian isolates, and in the phylogenetic analysis, they formed a distinct lineage within the Indian type 3 strains. This study indicates hyperendemicity of dengue in the region with the presence of multiple serotypes and high rates of co-infection, and local genomic evolution of the viral strains involved in this outbreak.

  17. Invited commentary: Dengue lessons from Cuba.

    PubMed

    Vaughn, D W

    2000-11-01

    An 18-year interval between a dengue virus type 1 outbreak in 1977-1979 and a dengue virus type 2 outbreak in 1997 in Santiago de Cuba, Cuba, provided a unique opportunity to evaluate risk factors for dengue disease. All patients with symptomatic dengue, including 205 cases of dengue hemorrhagic fever and 12 deaths, were adults born before the dengue virus type 1 epidemic, and nearly all (98%) experienced secondary dengue virus infections. In contrast, almost all of those who seroconverted without illness (97%) experienced primary dengue virus infection. This provides epidemiologic support for the immune enhancement theory of dengue pathogenesis. The Cuban experience suggests that immune enhancement can be seen even 20 years after the primary dengue virus infection. It also supports the contention that primary infections with dengue virus type 2 (and dengue virus type 4) are largely subclinical. These observations have implications for dengue vaccine development based on live-attenuated viruses.

  18. 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. PMID:26965962

  19. 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.

  20. Acute focal infections of dental origin.

    PubMed

    Olsen, Ingar; van Winkelhoff, Arie J

    2014-06-01

    This article describes the most important pus-producing acute oral infections (dental infections) that can spread extra-orally. Most of these infections are spread by bacteria entering the bloodstream. However, dental infections have a number of other pathways for dissemination. By forming abscesses or phlegmon they can reach facial spaces that communicate with each other and then spread downwards to the mediastinum or upwards to the brain. In such cases dental infections can become, if not properly treated, life-threatening. It seems that early diagnosis and treatment are imperative, and potentially infectious foci should be traced and eliminated. Dental hygiene and prophylaxis to prevent dental biofilm formation are important measures to reduce the risk of these calamities. The more compromised the host defense is, the more importance should be put on these measures. Although commensal bacteria are often involved in these infections, attention should also be paid to specific periodontal pathogens, and a proper microbial diagnosis, obtained using molecular methods plus bacterial sensitivity testing, can provide the patient with optimal care. Drainage of pus must be established where possible so that the optimal effect of antibiotics can be achieved. Penicillin is still the drug of first choice in settings where suspicion of methicillin-resistant Staphylococcus aureus is low.

  1. Acute focal infections of dental origin.

    PubMed

    Olsen, Ingar; van Winkelhoff, Arie J

    2014-06-01

    This article describes the most important pus-producing acute oral infections (dental infections) that can spread extra-orally. Most of these infections are spread by bacteria entering the bloodstream. However, dental infections have a number of other pathways for dissemination. By forming abscesses or phlegmon they can reach facial spaces that communicate with each other and then spread downwards to the mediastinum or upwards to the brain. In such cases dental infections can become, if not properly treated, life-threatening. It seems that early diagnosis and treatment are imperative, and potentially infectious foci should be traced and eliminated. Dental hygiene and prophylaxis to prevent dental biofilm formation are important measures to reduce the risk of these calamities. The more compromised the host defense is, the more importance should be put on these measures. Although commensal bacteria are often involved in these infections, attention should also be paid to specific periodontal pathogens, and a proper microbial diagnosis, obtained using molecular methods plus bacterial sensitivity testing, can provide the patient with optimal care. Drainage of pus must be established where possible so that the optimal effect of antibiotics can be achieved. Penicillin is still the drug of first choice in settings where suspicion of methicillin-resistant Staphylococcus aureus is low. PMID:24738592

  2. Immunomodulating and antiviral activities of Uncaria tomentosa on human monocytes infected with Dengue Virus-2.

    PubMed

    Reis, Sonia Regina I N; Valente, Ligia M M; Sampaio, André L; Siani, Antonio C; Gandini, Mariana; Azeredo, Elzinandes L; D'Avila, Luiz A; Mazzei, José L; Henriques, Maria das Graças M; Kubelka, Claire F

    2008-03-01

    Uncaria tomentosa (Willd.) DC., a large woody vine