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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Role of T cells, cytokines and antibody in dengue fever and dengue haemorrhagic fever.

PubMed

Fink, Joshua; Gu, Feng; Vasudevan, Subhash G

2006-01-01

Dengue infections are a major cause of morbidity and mortality in the tropical and sub-tropical regions of the world. There is no vaccine for dengue and also there are no anti-viral drugs to treat the infection. Some patients, typically those experiencing a secondary infection with a different dengue serotype, may progress from an acute febrile disease to the more severe forms of disease, dengue haemorrhagic fever and dengue shock syndrome. Here we discuss the significant immunopathological component to severe disease and how T cells, cytokines and cross-reactive antibody combine to contribute to the progression to dengue haemorrhagic fever. These events are thought to lead to vascular leakage, the signature event in dengue haemorrhagic fever, and are addressed in this review by incorporating the concept of heterologous T cell immunity. The need for effective measures against dengue and dengue-related illness is clear. We propose that drugs against dengue virus, or the symptoms of severe dengue disease, are a viable goal.

Surveillance for dengue and dengue-associated neurologic syndromes in the United States.

PubMed

Waterman, Stephen H; Margolis, Harold S; Sejvar, James J

2015-05-01

Autochthonous dengue virus transmission has occurred in the continental United States with increased frequency during the last decade; the principal vector, Aedes aegypti, has expanded its geographic distribution in the southern United States. Dengue, a potentially fatal arboviral disease, is underreported, and US clinicians encountering patients with acute febrile illness consistent with dengue are likely to not be fully familiar with dengue diagnosis and management. Recently, investigators suggested that an outbreak of dengue likely occurred in Houston during 2003 based on retrospective laboratory testing of hospitalized cases with encephalitis and aseptic meningitis. Although certain aspects of the Houston testing results and argument for local transmission are doubtful, the report highlights the importance of prospective surveillance for dengue in Aedes-infested areas of the United States, the need for clinical training on dengue and its severe manifestations, and the need for laboratory testing in domestic patients presenting with febrile neurologic illness in these regions to include dengue. © The American Society of Tropical Medicine and Hygiene.

Surveillance for Dengue and Dengue-Associated Neurologic Syndromes in the United States

PubMed Central

Waterman, Stephen H.; Margolis, Harold S.; Sejvar, James J.

2015-01-01

Autochthonous dengue virus transmission has occurred in the continental United States with increased frequency during the last decade; the principal vector, Aedes aegypti, has expanded its geographic distribution in the southern United States. Dengue, a potentially fatal arboviral disease, is underreported, and US clinicians encountering patients with acute febrile illness consistent with dengue are likely to not be fully familiar with dengue diagnosis and management. Recently, investigators suggested that an outbreak of dengue likely occurred in Houston during 2003 based on retrospective laboratory testing of hospitalized cases with encephalitis and aseptic meningitis. Although certain aspects of the Houston testing results and argument for local transmission are doubtful, the report highlights the importance of prospective surveillance for dengue in Aedes-infested areas of the United States, the need for clinical training on dengue and its severe manifestations, and the need for laboratory testing in domestic patients presenting with febrile neurologic illness in these regions to include dengue. PMID:25371183

Concurrent dengue and malaria infection in Lahore, Pakistan during the 2012 dengue outbreak.

PubMed

Assir, Muhammad Zaman Khan; Masood, Muhammad Adnan; Ahmad, Hafiz Ijaz

2014-01-01

We conducted this study to determine the frequency of malaria and dengue-malaria co-infection in patients admitted to our hospital as 'probable' cases of dengue fever during the 2012 outbreak of dengue, and to ascertain whether dengue-malaria co-infection was more severe than either infection alone. This cross-sectional observational study was conducted at Jinnah Hospital Lahore, Pakistan between August and November 2012. Patients with 2-10 days of fever and with two or more of the following: myalgia, arthralgia, retro-orbital pain, headache, skin rash, and hemorrhagic manifestations plus thrombocytopenia and leukopenia, were classified as probable cases of dengue fever and were subjected to reverse transcriptase (RT)-PCR and/or dengue-specific IgM by ELISA. The diagnosis of malaria was established on thick and thin blood film microscopy. Severe disease was defined by the presence of an altered level of consciousness, World Health Organization grade ≥2 bleeding, jaundice, circulatory shock, hemoglobin <50g/l, platelet count <50×10(9)/l, serum creatinine >265μmol/l, or death. There were 85 probable cases of dengue fever. Sixty-four (75%) were male and the median age was 22 years (range 12-90 years). Of 52 patients for whom results of diagnostic tests for both dengue and malaria were available, five (10%) had isolated dengue infection, 18 (35%) isolated Plasmodium infection, and 17 (33%) dengue-malaria co-infection. Thirty-five out of 52 (67%) probable cases had malaria and 17 out of 22 (77%) dengue-specific IgM reactive patients had concurrent malaria. Patients with isolated malaria had significantly lower median hemoglobin concentrations (124.5g/l vs. 144.0 g/l, p = 0.04) and median hematocrit (36.0 vs. 41.7, p=0.02) at presentation than cases of isolated dengue. Patients with dengue-malaria co-infection had a significantly lower rate of jaundice than those with isolated dengue (0% vs. 40%, p = 0.04). The frequency of severe disease was comparable amongst the

DengueTools: innovative tools and strategies for the surveillance and control of dengue

PubMed Central

Wilder-Smith, Annelies; Renhorn, Karl-Erik; Tissera, Hasitha; Abu Bakar, Sazaly; Alphey, Luke; Kittayapong, Pattamaporn; Lindsay, Steve; Logan, James; Hatz, Christoph; Reiter, Paul; Rocklöv, Joacim; Byass, Peter; Louis, Valérie R.; Tozan, Yesim; Massad, Eduardo; Tenorio, Antonio; Lagneau, Christophe; L'Ambert, Grégory; Brooks, David; Wegerdt, Johannah; Gubler, Duane

2012-01-01

Dengue fever is a mosquito-borne viral disease estimated to cause about 230 million infections worldwide every year, of which 25,000 are fatal. Global incidence has risen rapidly in recent decades with some 3.6 billion people, over half of the world's population, now at risk, mainly in urban centres of the tropics and subtropics. Demographic and societal changes, in particular urbanization, globalization, and increased international travel, are major contributors to the rise in incidence and geographic expansion of dengue infections. Major research gaps continue to hamper the control of dengue. The European Commission launched a call under the 7th Framework Programme with the title of ‘Comprehensive control of Dengue fever under changing climatic conditions’. Fourteen partners from several countries in Europe, Asia, and South America formed a consortium named ‘DengueTools’ to respond to the call to achieve better diagnosis, surveillance, prevention, and predictive models and improve our understanding of the spread of dengue to previously uninfected regions (including Europe) in the context of globalization and climate change. The consortium comprises 12 work packages to address a set of research questions in three areas: Research area 1: Develop a comprehensive early warning and surveillance system that has predictive capability for epidemic dengue and benefits from novel tools for laboratory diagnosis and vector monitoring. Research area 2: Develop novel strategies to prevent dengue in children. Research area 3: Understand and predict the risk of global spread of dengue, in particular the risk of introduction and establishment in Europe, within the context of parameters of vectorial capacity, global mobility, and climate change. In this paper, we report on the rationale and specific study objectives of ‘DengueTools’. DengueTools is funded under the Health theme of the Seventh Framework Programme of the European Community, Grant Agreement Number: 282589

DengueTools: innovative tools and strategies for the surveillance and control of dengue.

PubMed

Wilder-Smith, Annelies; Renhorn, Karl-Erik; Tissera, Hasitha; Abu Bakar, Sazaly; Alphey, Luke; Kittayapong, Pattamaporn; Lindsay, Steve; Logan, James; Hatz, Christoph; Reiter, Paul; Rocklöv, Joacim; Byass, Peter; Louis, Valérie R; Tozan, Yesim; Massad, Eduardo; Tenorio, Antonio; Lagneau, Christophe; L'Ambert, Grégory; Brooks, David; Wegerdt, Johannah; Gubler, Duane

2012-01-01

Dengue fever is a mosquito-borne viral disease estimated to cause about 230 million infections worldwide every year, of which 25,000 are fatal. Global incidence has risen rapidly in recent decades with some 3.6 billion people, over half of the world's population, now at risk, mainly in urban centres of the tropics and subtropics. Demographic and societal changes, in particular urbanization, globalization, and increased international travel, are major contributors to the rise in incidence and geographic expansion of dengue infections. Major research gaps continue to hamper the control of dengue. The European Commission launched a call under the 7th Framework Programme with the title of 'Comprehensive control of Dengue fever under changing climatic conditions'. Fourteen partners from several countries in Europe, Asia, and South America formed a consortium named 'DengueTools' to respond to the call to achieve better diagnosis, surveillance, prevention, and predictive models and improve our understanding of the spread of dengue to previously uninfected regions (including Europe) in the context of globalization and climate change.The consortium comprises 12 work packages to address a set of research questions in three areas:Research area 1: Develop a comprehensive early warning and surveillance system that has predictive capability for epidemic dengue and benefits from novel tools for laboratory diagnosis and vector monitoring.Research area 2: Develop novel strategies to prevent dengue in children.Research area 3: Understand and predict the risk of global spread of dengue, in particular the risk of introduction and establishment in Europe, within the context of parameters of vectorial capacity, global mobility, and climate change.In this paper, we report on the rationale and specific study objectives of 'DengueTools'. DengueTools is funded under the Health theme of the Seventh Framework Programme of the European Community, Grant Agreement Number: 282589 Dengue Tools.

Virulence Markers of Dengue Viruses

DTIC Science & Technology

1990-02-20

of dengue viruses . We initially evaluated onocye-infectivity as a marker the for virulence of dengue-2 virus by testing 72 dengue-2 viral isolates...infectivity can be used as a virulence marker for dengue viruses . For this purpose, virulence is defined as the intrinsic ability of the virus to...but not dengue-1 and -3 viruses Table 5. Comparison of infectivity of dengue-2 virus in K-562 28 monocytes and viral monocyte infectivity index derived

Dengue fever and dengue haemorrhagic fever in adolescents and adults

PubMed Central

Tantawichien, Terapong

2012-01-01

Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a paediatric disease, the age distribution of dengue has been rising and more cases have been observed in adolescents and adults. Furthermore, the development of tourism in the tropics has led to an increase in the number of tourists who become infected, most of whom are adults. Symptoms and risk factors for dengue haemorrhagic fever (DHF) and severe dengue differ between children and adults, with co-morbidities and incidence in more elderly patients associated with greater risk of mortality. Treatment options for DF and DHF in adults, as for children, centre round fluid replacement (either orally or intravenously, depending on severity) and antipyretics. Further data are needed on the optimal treatment of adult patients. PMID:22668446

Climate variation drives dengue dynamics

PubMed Central

Xu, Lei; Stige, Leif C.; Chan, Kung-Sik; Zhou, Jie; Yang, Jun; Sang, Shaowei; Wang, Ming; Yang, Zhicong; Yan, Ziqiang; Jiang, Tong; Lu, Liang; Yue, Yujuan; Liu, Xiaobo; Lin, Hualiang; Xu, Jianguo; Liu, Qiyong; Stenseth, Nils Chr.

2017-01-01

Dengue, a viral infection transmitted between people by mosquitoes, is one of the most rapidly spreading diseases in the world. Here, we report the analyses covering 11 y (2005–2015) from the city of Guangzhou in southern China. Using the first 8 y of data to develop an ecologically based model for the dengue system, we reliably predict the following 3 y of dengue dynamics—years with exceptionally extensive dengue outbreaks. We demonstrate that climate conditions, through the effects of rainfall and temperature on mosquito abundance and dengue transmission rate, play key roles in explaining the temporal dynamics of dengue incidence in the human population. Our study thus contributes to a better understanding of dengue dynamics and provides a predictive tool for preventive dengue reduction strategies. PMID:27940911

Human Immune Response to Dengue Infections

DTIC Science & Technology

1989-07-31

antigens of all 4 serotypes. These CTL lysed autologous fibroblasts infected with vaccinia-dengue recombinant viruses containing the E, or several non...responses of PBMC from a dengue 4-immune donor to call-free dengue viruses . .. ........... 6 Table 2. Lysis of dengue virus-infected fibroblasts by dengue...4-immune PBMC stimulated with dengue viruses ... ...... 7 Table 3. Inhibition of the lysis of dengue- infected fibroblasts by monoclonal anti-CD8

Dengue Virus 3 Genotype 1 Associated with Dengue Fever and Dengue Hemorrhagic Fever, Brazil

PubMed Central

Figueiredo, Leandra Barcelos; Cecílio, Alzira Batista; Ferreira, Gustavo Portela; Drumond, Betânia Paiva; Germano de Oliveira, Jaquelline; Bonjardim, Cláudio Antônio; Ferreira, Paulo César Peregrino

2008-01-01

Dengue serotype 3 viruses were isolated from patients in Brazil from 2002 through 2004. On the basis of phylogenetic analyses, these isolates were assigned genotype 1. This genotype had never been reported in South America before. Its appearance indicates a major risk factor for dengue epidemics and severe disease. PMID:18258129

Dengue reemergence in Argentina.

PubMed Central

Avilés, G.; Rangeón, G.; Vorndam, V.; Briones, A.; Baroni, P.; Enria, D.; Sabattini, M. S.

1999-01-01

Aedes aegypti, eradicated from Argentina in 1963, has now reinfested the country as far south as Buenos Aires. In 1997, four persons with travel histories to Brazil, Ecuador, or Venezuela had confirmed dengue, and surveillance for indigenous transmission allowed the detection of 19 dengue cases in Salta Province. These cases of dengue are the first in Argentina since 1916 and represent a new southern extension of dengue virus. PMID:10460181

Development of an anti-dengue NS1 IgG ELISA to evaluate exposure to dengue virus.

PubMed

Nascimento, Eduardo J M; George, James K; Velasco, Melissa; Bonaparte, Matthew I; Zheng, Lingyi; DiazGranados, Carlos A; Marques, Ernesto T A; Huleatt, James W

2018-07-01

Dengue virus infection elicits immune responses to multiple viral antigens including antibodies to dengue non-structural protein 1 (NS1) which are rapidly induced and detected within days of infection. The recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV; Sanofi Pasteur) uses the yellow fever vaccine virus as a back-bone but expresses dengue virus pre-membrane and envelop proteins. Since CYD-TDV does not express dengue NS1, we evaluated the utility of dengue NS1-specific IgG antibodies as biomarkers of dengue exposure in CYD-TDV recipients and controls. We optimized and evaluated a quantitative anti-dengue NS1 IgG enzyme-linked immunosorbent assay (ELISA). Parameters assessed included: accuracy, dilutability/linearity, precision, limit of quantitation and specificity. The assay specificity was further evaluated using Japanese Encephalitis virus, West Nile virus, Yellow Fever virus or Zika virus positive sera samples collected following confirmed infection or vaccination. Receiver-operating-characteristics (ROC) curves as well as sensitivity and specificity for discriminating previous dengue exposure were assessed using 1250 reference samples. Overall, the anti-dengue NS1 IgG ELISA was able to discriminate previous dengue exposure from non-exposure before vaccination with CYD-TDV (ROC area under the curve > 0.9). Assessment of paired samples from 2511 vaccinated participants showed high overall agreement (93%) between pre-vaccination and post-vaccination dengue serostatus classification based on the anti-dengue NS1 IgG ELISA. However, misclassification of dengue serostatus was observed after vaccination likely due to a combination of asymptomatic dengue infections, assay variability and a modest effect of CYD-TDV on the anti-dengue NS1 IgG ELISA readout. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Dengue Virus Seroconversion in Travelers to Dengue-Endemic Areas

PubMed Central

Olivero, Rosemary M.; Hamer, Davidson H.; MacLeod, William B.; Benoit, Christine M.; Sanchez-Vegas, Carolina; Jentes, Emily S.; Chen, Lin H.; Wilson, Mary E.; Marano, Nina; Yanni, Emad A.; Ooi, Winnie W.; Karchmer, Adolf W.; Kogelman, Laura; Barnett, Elizabeth D.

2016-01-01

We conducted a prospective study to measure dengue virus (DENV) antibody seroconversion in travelers to dengue-endemic areas. Travelers seen in the Boston Area Travel Medicine Network planning to visit dengue-endemic countries for ≥ 2 weeks were enrolled from 2009 to 2010. Pre- and post-travel blood samples and questionnaires were collected. Post-travel sera were tested for anti-DENV IgG by indirect IgG enzyme-linked immunosorbent assay (ELISA) and anti-DENV IgM by capture IgM ELISA. Participants with positive post-travel anti-DENV IgG or IgM were tested for pre-travel anti-DENV IgG and IgM; they were excluded from the seroconversion calculation if either pre-travel anti-DENV IgG or IgM were positive. Paired sera and questionnaires were collected for 62% (589/955) of enrolled travelers. Most participants were 19–64 years of age, female, and white. The most common purposes of travel were tourism and visiting friends and relatives; most trips were to Asia or Africa. Median length of travel was 21 days. DENV antibody seroconversion by either anti-DENV IgM or IgG ELISA was 2.9–6.8%; lower range percent excluded potential false-positive anti-DENV IgG due to receipt of yellow fever or Japanese encephalitis vaccines at enrollment; upper range percent excluded proven false-positive anti-DENV IgM. Eighteen percent of those with seroconversion reported dengue-like symptoms. Seroconversion was documented for travel to Africa as well as countries and regions known to be highly dengue endemic (India, Brazil, southeast Asia). Given widespread risk of dengue, travel medicine counseling should include information on risk of dengue in endemic areas and advice on preventing insect bites and seeking prompt medical attention for febrile illness. PMID:27573631

Role of cognitive parameters in dengue hemorrhagic fever and dengue shock syndrome

PubMed Central

2013-01-01

Dengue is becoming recognized as one of the most important vector-borne human diseases. It is predominant in tropical and subtropical zones but its geographical distribution is progressively expanding, making it an escalating global health problem of today. Dengue presents with spectrum of clinical manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life-threatening illness characterized by plasma leakage due to increased vascular permeability. Currently, there are no antiviral modalities or vaccines available to treat and prevent dengue. Supportive care with close monitoring is the standard clinical practice. The mechanisms leading to DHF/DSS remains poorly understood. Multiple factors have been attributed to the pathological mechanism, but only a couple of these hypotheses are popular in scientific circles. The current discussion focuses on underappreciated factors, temperature, natural IgM, and endotoxin, which may be critical components playing roles in dengue pathogenesis. PMID:24305068

Best Practices in Dengue Surveillance: A Report from the Asia-Pacific and Americas Dengue Prevention Boards

PubMed Central

Beatty, Mark E.; Stone, Amy; Fitzsimons, David W.; Hanna, Jeffrey N.; Lam, Sai Kit; Vong, Sirenda; Guzman, Maria G.; Mendez-Galvan, Jorge F.; Halstead, Scott B.; Letson, G. William; Kuritsky, Joel; Mahoney, Richard; Margolis, Harold S.

2010-01-01

Background Dengue fever is a virus infection that is spread by the Aedes aegypti mosquito and can cause severe disease especially in children. Dengue fever is a major problem in tropical and sub-tropical regions of the world. Methodology/Principal Findings We invited dengue experts from around the world to attend meetings to discuss dengue surveillance. We reviewed literature, heard detailed reports on surveillance programs, and shared expert opinions. Results Presentations by 22 countries were heard during the 2.5 day meetings. We describe the best methods of surveillance in general, the stakeholders in dengue surveillance, and the steps from mosquito bite to reporting of a dengue case to explore how best to carry out dengue surveillance. We also provide details and a comparison of the dengue surveillance programs by the presenting countries. Conclusions/Significance The experts provided recommendations for achieving the best possible data from dengue surveillance accepting the realities of the real world (e.g., limited funding and staff). Their recommendations included: (1) Every dengue endemic country should make reporting of dengue cases to the government mandatory; (2) electronic reporting systems should be developed and used; (3) at minimum dengue surveillance data should include incidence, hospitalization rates, deaths by age group; (4) additional studies should be completed to check the sensitivity of the system; (5) laboratories should share expertise and data; (6) tests that identify dengue virus should be used in patients with fever for four days or less and antibody tests should be used after day 4 to diagnose dengue; and (7) early detection and prediction of dengue outbreaks should be goals for national surveillance systems. PMID:21103381

Rhombencephalitis associated with Dengue fever.

PubMed

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

2016-05-01

Dengue infection is gradually disseminating throughout the world in alarming proportions. It is a arbovirus infection,transmitted by aedes mosquitoes. It is a multi-systemic disorder associated with varied neurological complications. There is increased trend of development of neurological complications in dengue fever. The neurological complications arising due to dengue infection can be categorized into central and neuromuscular complications. The central nervous system disorders reported with dengue fever are encephalopathy,encephalitis and myelitis.Here we report a case of rhombencephalitis associated with dengue fever. The literature does not mention rhombencephalitis occurring with dengue illness. Copyright © 2016 Elsevier B.V. All rights reserved.

Dengue in Bali: Clinical characteristics and genetic diversity of circulating dengue viruses.

PubMed

Megawati, Dewi; Masyeni, Sri; Yohan, Benediktus; Lestarini, Asri; Hayati, Rahma F; Meutiawati, Febrina; Suryana, Ketut; Widarsa, Tangking; Budiyasa, Dewa G; Budiyasa, Ngurah; Myint, Khin S A; Sasmono, R Tedjo

2017-05-01

A high number of dengue cases are reported annually in Bali. Despite the endemicity, limited data on dengue is available for Bali localities. Molecular surveillance study was conducted to explore the clinical and virological characteristics of dengue patients in urban Denpasar and rural Gianyar areas in Bali during the peak season in 2015. A total of 205 adult dengue-suspected patients were recruited in a prospective cross-sectional study. Demographic and clinical information were obtained, and dengue screening was performed using NS1 and IgM/IgG ELISAs. Viral RNA was subsequently extracted from patients' sera for serotyping using conventional RT-PCR and Simplexa Dengue real-time RT-PCR, followed by genotyping with sequencing method. We confirmed 161 patients as having dengue by NS1 and RT-PCR. Among 154 samples successfully serotyped, the DENV-3 was predominant, followed by DENV-1, DENV-2, and DENV-4. Serotype predominance was different between Denpasar and Gianyar. Genotyping results classify DENV-1 isolates into Genotype I and DENV-2 as Cosmopolitan Genotype. The classification grouped isolates into Genotype I and II for DENV-3 and DENV-4, respectively. Clinical parameters showed no relationship between infecting serotypes and severity. We observed the genetic diversity of circulating DENV isolates and their relatedness with historical data and importation to other countries. Our data highlights the role of this tourist destination as a potential source of dengue transmission in the region.

Dengue in Bali: Clinical characteristics and genetic diversity of circulating dengue viruses

PubMed Central

Yohan, Benediktus; Lestarini, Asri; Hayati, Rahma F.; Meutiawati, Febrina; Suryana, Ketut; Widarsa, Tangking; Budiyasa, Dewa G.; Budiyasa, Ngurah; Myint, Khin S. A.

2017-01-01

A high number of dengue cases are reported annually in Bali. Despite the endemicity, limited data on dengue is available for Bali localities. Molecular surveillance study was conducted to explore the clinical and virological characteristics of dengue patients in urban Denpasar and rural Gianyar areas in Bali during the peak season in 2015. A total of 205 adult dengue-suspected patients were recruited in a prospective cross-sectional study. Demographic and clinical information were obtained, and dengue screening was performed using NS1 and IgM/IgG ELISAs. Viral RNA was subsequently extracted from patients’ sera for serotyping using conventional RT-PCR and Simplexa Dengue real-time RT-PCR, followed by genotyping with sequencing method. We confirmed 161 patients as having dengue by NS1 and RT-PCR. Among 154 samples successfully serotyped, the DENV-3 was predominant, followed by DENV-1, DENV-2, and DENV-4. Serotype predominance was different between Denpasar and Gianyar. Genotyping results classify DENV-1 isolates into Genotype I and DENV-2 as Cosmopolitan Genotype. The classification grouped isolates into Genotype I and II for DENV-3 and DENV-4, respectively. Clinical parameters showed no relationship between infecting serotypes and severity. We observed the genetic diversity of circulating DENV isolates and their relatedness with historical data and importation to other countries. Our data highlights the role of this tourist destination as a potential source of dengue transmission in the region. PMID:28531223

Dengue fever.

PubMed

Skinner, Anita

Dengue fever is a notifiable infectious disease in England because of its geographic expansion and the increase in the number of epidemics. The article highlighted the importance of informing overseas travellers of the risk of acquiring dengue fever and advising them on personal protective measures.

Dengue: a continuing global threat

PubMed Central

Guzman, Maria G.; Halstead, Scott B.; Artsob, Harvey; Buchy, Philippe; Farrar, Jeremy; Gubler, Duane J.; Hunsperger, Elizabeth; Kroeger, Axel; Margolis, Harold S.; Martínez, Eric; Nathan, Michael B.; Pelegrino, Jose Luis; Simmons, Cameron; Yoksan, Sutee; Peeling, Rosanna W.

2014-01-01

Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ~50 million dengue infections and ~500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future. PMID:21079655

Is drought helping or killing dengue? Investigation of spatiotemporal relationship between dengue fever and drought

NASA Astrophysics Data System (ADS)

Lee, Chieh-Han; Yu, Hwa-Lung

2015-04-01

Dengue Fever is a vector-borne disease that is transmitted between human and mosquitos in tropical and sub-tropical regions. Previous studies have found significant relationship between the epidemic of dengue cases and climate variables, especially temperature and precipitation. Besides, the natural phenomena (e.g., drought) are considered that significantly drop the number of dengue cases by killing vector's breeding environment. However, in Kaohsiung City, Taiwan, there are evidences that the temporal pattern of dengue is correlated to drought events. Kaohsiung City experienced two main dengue outbreaks in 2002 and 2014 that both years were confirmed with serious drought. Especially in 2014, Kaohsiung City was suffered from extremely dengue outbreak in 2014 that reported the highest number of dengue cases in the history. This study constructs the spatiotemporal model of dengue incidences and index of drought events (Standardized Precipitation Index, SPI) based on the distributed lag nonlinear model (DLNM). Other meteorological measures are also included in the analysis.

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.

Controlling Dengue with Vaccines in Thailand

PubMed Central

Chao, Dennis L.; Halstead, Scott B.; Halloran, M. Elizabeth; Longini, Ira M.

2012-01-01

Background Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently being tested in clinical trials. Before the widespread introduction of a new dengue vaccine, one needs to consider how best to use limited supplies of vaccine given the complex dengue transmission dynamics and the immunological interaction among the four dengue serotypes. Methodology/Principal Findings We developed an individual-level (including both humans and mosquitoes), stochastic simulation model for dengue transmission and control in a semi-rural area in Thailand. We calibrated the model to dengue serotype-specific infection, illness and hospitalization data from Thailand. Our simulations show that a realistic roll-out plan, starting with young children then covering progressively older individuals in following seasons, could reduce local transmission of dengue to low levels. Simulations indicate that this strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue hospitalizations per 100,000 people at risk over a ten-year period. Conclusions/Significance Vaccination will have an important role in controlling dengue. According to our modeling results, children should be prioritized to receive vaccine, but adults will also need to be vaccinated if one wants to reduce community-wide dengue transmission to low levels. PMID:23145197

Tri-phasic fever in dengue fever.

PubMed

D, Pradeepa H; Rao, Sathish B; B, Ganaraj; Bhat, Gopalakrishna; M, Chakrapani

2018-04-01

Dengue fever is an acute febrile illness with a duration of 2-12 days. Our observational study observed the 24-h continuous tympanic temperature pattern of 15 patients with dengue fever and compared this with 26 others with fever due to a non-dengue aetiology. A tri-phasic fever pattern was seen among two-thirds of dengue fever patients, but in only one with an inflammatory disease. One-third of dengue fever patients exhibited a single peak temperature. Continuous temperature monitoring and temperature pattern analysis in clinical settings can aid in the early differentiation of dengue fever from non-dengue aetiology.

Dengue Epidemiology

MedlinePlus

... 2.5 billion people, or 40% of the world’s population, live in areas where there is a risk of dengue transmission. Dengue is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. The World Health Organization (WHO) estimates that 50 to 100 ...

Prospects for dengue vaccines for travelers

PubMed Central

2016-01-01

Travel-acquired dengue cases have been increasing as the overall global dengue burden has expanded. In Korea, imported dengue cases have been reported since 2000 when it first became a notifiable disease. During the first four months of 2016, three times more dengue cases were reported in Korea than during the same period the previous year. A safe and efficacious vaccine for travelers would be beneficial to prevent dengue disease in individual travelers and potentially decrease the risk of virus spread to non-endemic areas. Here, we summarize the characteristics of dengue vaccines for travelers and review dengue vaccines currently licensed or in clinical development. PMID:27489798

Dengue fever (image)

MedlinePlus

Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

Clustering, climate and dengue transmission.

PubMed

Junxiong, Pang; Yee-Sin, Leo

2015-06-01

Dengue is currently the most rapidly spreading vector-borne disease, with an increasing burden over recent decades. Currently, neither a licensed vaccine nor an effective anti-viral therapy is available, and treatment largely remains supportive. Current vector control strategies to prevent and reduce dengue transmission are neither efficient nor sustainable as long-term interventions. Increased globalization and climate change have been reported to influence dengue transmission. In this article, we reviewed the non-climatic and climatic risk factors which facilitate dengue transmission. Sustainable and effective interventions to reduce the increasing threat from dengue would require the integration of these risk factors into current and future prevention strategies, including dengue vaccination, as well as the continuous support and commitment from the political and environmental stakeholders.

Cost-effectiveness of dengue vaccination in Yucatán, Mexico using a dynamic dengue transmission model

PubMed Central

Shim, Eunha

2017-01-01

Background The incidence of dengue fever (DF) is steadily increasing in Mexico, burdening health systems with consequent morbidities and mortalities. On December 9th, 2015, Mexico became the first country for which the dengue vaccine was approved for use. In anticipation of a vaccine rollout, analysis of the cost-effectiveness of the dengue vaccination program that quantifies the dynamics of disease transmission is essential. Methods We developed a dynamic transmission model of dengue in Yucatán, Mexico and its proposed vaccination program to incorporate herd immunity into our analysis of cost-effectiveness analysis. Our model also incorporates important characteristics of dengue epidemiology, such as clinical cross-immunity and susceptibility enhancement upon secondary infection. Using our model, we evaluated the cost-effectiveness and economic impact of an imperfect dengue vaccine in Yucatán, Mexico. Conclusions Our study indicates that a dengue vaccination program would prevent 90% of cases of symptomatic DF incidence as well as 90% of dengue hemorrhagic fever (DHF) incidence and dengue-related deaths annually. We conclude that a dengue vaccine program in Yucatán, Mexico would be very cost-effective as long as the vaccination cost per individual is less than $140 and $214 from health care and societal perspectives, respectively. Furthermore, at an exemplary vaccination cost of $250 USD per individual on average, dengue vaccination is likely to be cost-effective 43% and 88% of the time from health care and societal perspectives, respectively. PMID:28380060

Cost-effectiveness of dengue vaccination in Yucatán, Mexico using a dynamic dengue transmission model.

PubMed

Shim, Eunha

2017-01-01

The incidence of dengue fever (DF) is steadily increasing in Mexico, burdening health systems with consequent morbidities and mortalities. On December 9th, 2015, Mexico became the first country for which the dengue vaccine was approved for use. In anticipation of a vaccine rollout, analysis of the cost-effectiveness of the dengue vaccination program that quantifies the dynamics of disease transmission is essential. We developed a dynamic transmission model of dengue in Yucatán, Mexico and its proposed vaccination program to incorporate herd immunity into our analysis of cost-effectiveness analysis. Our model also incorporates important characteristics of dengue epidemiology, such as clinical cross-immunity and susceptibility enhancement upon secondary infection. Using our model, we evaluated the cost-effectiveness and economic impact of an imperfect dengue vaccine in Yucatán, Mexico. Our study indicates that a dengue vaccination program would prevent 90% of cases of symptomatic DF incidence as well as 90% of dengue hemorrhagic fever (DHF) incidence and dengue-related deaths annually. We conclude that a dengue vaccine program in Yucatán, Mexico would be very cost-effective as long as the vaccination cost per individual is less than $140 and $214 from health care and societal perspectives, respectively. Furthermore, at an exemplary vaccination cost of $250 USD per individual on average, dengue vaccination is likely to be cost-effective 43% and 88% of the time from health care and societal perspectives, respectively.

Ensemble method for dengue prediction

PubMed Central

Baugher, Benjamin; Moniz, Linda J.; Bagley, Thomas; Babin, Steven M.; Guven, Erhan

2018-01-01

Background In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico) during four dengue seasons: 1) peak height (i.e., maximum weekly number of cases during a transmission season; 2) peak week (i.e., week in which the maximum weekly number of cases occurred); and 3) total number of cases reported during a transmission season. A dengue transmission season is the 12-month period commencing with the location-specific, historical week with the lowest number of cases. At the beginning of the Dengue Challenge, participants were provided with the same input data for developing the models, with the prediction testing data provided at a later date. Methods Our approach used ensemble models created by combining three disparate types of component models: 1) two-dimensional Method of Analogues models incorporating both dengue and climate data; 2) additive seasonal Holt-Winters models with and without wavelet smoothing; and 3) simple historical models. Of the individual component models created, those with the best performance on the prior four years of data were incorporated into the ensemble models. There were separate ensembles for predicting each of the three targets at each of the two locations. Principal findings Our ensemble models scored higher for peak height and total dengue case counts reported in a transmission season for Iquitos than all other models submitted to the Dengue Challenge. However, the ensemble models did not do nearly as well when predicting the peak week. Conclusions The Dengue Challenge organizers scored the dengue predictions of the Challenge participant groups. Our ensemble approach was the best in predicting the total number of dengue cases reported for transmission season and peak height for Iquitos, Peru. PMID:29298320

Ensemble method for dengue prediction.

PubMed

Buczak, Anna L; Baugher, Benjamin; Moniz, Linda J; Bagley, Thomas; Babin, Steven M; Guven, Erhan

2018-01-01

In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico) during four dengue seasons: 1) peak height (i.e., maximum weekly number of cases during a transmission season; 2) peak week (i.e., week in which the maximum weekly number of cases occurred); and 3) total number of cases reported during a transmission season. A dengue transmission season is the 12-month period commencing with the location-specific, historical week with the lowest number of cases. At the beginning of the Dengue Challenge, participants were provided with the same input data for developing the models, with the prediction testing data provided at a later date. Our approach used ensemble models created by combining three disparate types of component models: 1) two-dimensional Method of Analogues models incorporating both dengue and climate data; 2) additive seasonal Holt-Winters models with and without wavelet smoothing; and 3) simple historical models. Of the individual component models created, those with the best performance on the prior four years of data were incorporated into the ensemble models. There were separate ensembles for predicting each of the three targets at each of the two locations. Our ensemble models scored higher for peak height and total dengue case counts reported in a transmission season for Iquitos than all other models submitted to the Dengue Challenge. However, the ensemble models did not do nearly as well when predicting the peak week. The Dengue Challenge organizers scored the dengue predictions of the Challenge participant groups. Our ensemble approach was the best in predicting the total number of dengue cases reported for transmission season and peak height for Iquitos, Peru.

Dengue and dengue hemorrhagic fever in the Americas: lessons and challenges.

PubMed

Guzman, María G; Kouri, Gustavo

2003-05-01

The incidence of dengue and dengue hemorrhagic fever (DF/DHF) has increased significantly over the last decades. Yearly, an estimated 50-100 million cases of DF and about 250000-500000 cases of DHF occur worldwide. The epidemiological situation in Latin America now resembles that in Southeast Asia. Here, the main clinical, epidemiological and virological observations in the American region are presented and compared with those previously reported from Southeast Asia. During 2002, more than 30 Latin American countries reported over 1000000 DF cases. DHF occurred in 20 countries with more than 17000 DHF cases, including 225 fatalities. The co-circulation of multiple serotypes has been reported from many countries. In the Americas, DHF is observed both in children and adults; secondary infection by a different dengue virus serotype has been confirmed as an important risk factor for this severe form of the disease. However, some new risk factors such as the interval of dengue virus infections and the ethnicity and underlying chronic conditions of the patient have also been identified. The sequence of dengue virus infections and association with certain genotypes are further factors of importance. We also discuss the control and prevention strategies. In conclusion, without urgent action for the prevention and control of dengue/DHF and its vector, the current situation will worsen and, more dramatical, there is a risk of the urbanization of yellow fever.

Symptomatic Dengue Disease in Five Southeast Asian Countries: Epidemiological Evidence from a Dengue Vaccine Trial.

PubMed

Nealon, Joshua; Taurel, Anne-Frieda; Capeding, Maria Rosario; Tran, Ngoc Huu; Hadinegoro, Sri Rezeki; Chotpitayasunondh, Tawee; Chong, Chee Kheong; Wartel, T Anh; Beucher, Sophie; Frago, Carina; Moureau, Annick; Simmerman, Mark; Laot, Thelma; L'Azou, Maïna; Bouckenooghe, Alain

2016-08-01

Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2-14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14's active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions.

Symptomatic Dengue Disease in Five Southeast Asian Countries: Epidemiological Evidence from a Dengue Vaccine Trial

PubMed Central

Taurel, Anne-Frieda; Capeding, Maria Rosario; Tran, Ngoc Huu; Hadinegoro, Sri Rezeki; Chotpitayasunondh, Tawee; Chong, Chee Kheong; Wartel, T. Anh; Beucher, Sophie; Frago, Carina; Moureau, Annick; Simmerman, Mark; Laot, Thelma; L’Azou, Maïna; Bouckenooghe, Alain

2016-01-01

Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2–14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14’s active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions. PMID:27532617

Neurological Manifestations of Dengue Infection.

PubMed

Li, Guo-Hong; Ning, Zhi-Jie; Liu, Yi-Ming; Li, Xiao-Hong

2017-01-01

Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS), peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

Human Immune Response to Dengue Infections

DTIC Science & Technology

1991-06-30

had been immunized with yellow fever vaccine and later became infected with dengue 3 virus, responded best to dengue 3 antigen but also responded to...effective dengue virus subunit vaccines . We found evidence of marked T cell activation in patients with DHF. T cell activation in patients with DF was similar...Treatment and Control of Dengue Hemorrhagic Fever. World Health Organization, Geneva, Switzerland 7. Sabin AB (1952) Research on dengue during World

Reviewing Dengue: Still a Neglected Tropical Disease?

PubMed Central

Horstick, Olaf; Tozan, Yesim; Wilder-Smith, Annelies

2015-01-01

Dengue is currently listed as a “neglected tropical disease” (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003–2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD. PMID:25928673

Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue.

PubMed

Fragnoud, Romain; Flamand, Marie; Reynier, Frederic; Buchy, Philippe; Duong, Vasna; Pachot, Alexandre; Paranhos-Baccala, Glaucia; Bedin, Frederic

2015-11-14

Dengue is the most widespread mosquito-borne viral disease of public health concern. In some patients, endothelial cell and platelet dysfunction lead to life-threatening hemorrhagic dengue fever or dengue shock syndrome. Prognostication of disease severity is urgently required to improve patient management. The pathogenesis of severe dengue has not been fully elucidated, and the role of host proteins associated with viral particles has received little exploration. The proteomes of virion-enriched fractions purified from plasma pools of patients with dengue fever or severe dengue were compared. Virions were purified by ultracentrifugation combined with a water-insoluble polyelectrolyte-based technique. Following in-gel hydrolysis, peptides were analyzed by nano-liquid chromatography coupled to ion trap mass spectrometry and identified using data libraries. Both dengue fever and severe dengue viral-enriched fractions contained identifiable viral envelope proteins and host cellular proteins. Canonical pathway analysis revealed the identified host proteins are mainly involved in the coagulation cascade, complement pathway or acute phase response signaling pathway. Some host proteins were over- or under-represented in plasma from patients with severe dengue compared to patients with dengue fever. ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. Among 22 host proteins tested, two could differentiate between dengue fever and severe dengue in two independent cohorts (olfactomedin-4: area under the curve (AUC), 0.958; and platelet factor-4: AUC, 0.836). A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. The impact of these host proteins on pathogenicity and disease outcome

Climate and dengue transmission: evidence and implications.

PubMed

Morin, Cory W; Comrie, Andrew C; Ernst, Kacey

2013-01-01

Climate influences dengue ecology by affecting vector dynamics, agent development, and mosquito/human interactions. Although these relationships are known, the impact climate change will have on transmission is unclear. Climate-driven statistical and process-based models are being used to refine our knowledge of these relationships and predict the effects of projected climate change on dengue fever occurrence, but results have been inconsistent. We sought to identify major climatic influences on dengue virus ecology and to evaluate the ability of climate-based dengue models to describe associations between climate and dengue, simulate outbreaks, and project the impacts of climate change. We reviewed the evidence for direct and indirect relationships between climate and dengue generated from laboratory studies, field studies, and statistical analyses of associations between vectors, dengue fever incidence, and climate conditions. We assessed the potential contribution of climate-driven, process-based dengue models and provide suggestions to improve their performance. Relationships between climate variables and factors that influence dengue transmission are complex. A climate variable may increase dengue transmission potential through one aspect of the system while simultaneously decreasing transmission potential through another. This complexity may at least partly explain inconsistencies in statistical associations between dengue and climate. Process-based models can account for the complex dynamics but often omit important aspects of dengue ecology, notably virus development and host-species interactions. Synthesizing and applying current knowledge of climatic effects on all aspects of dengue virus ecology will help direct future research and enable better projections of climate change effects on dengue incidence.

Human Immune Response to Dengue Infections

DTIC Science & Technology

1990-07-31

flavivirus-crossreactive clone recognized dengue-l, -2, -3, and -4 virus and West Nile virus (WNV), but did not recognize yellow fever virus ( YFV ), while...three flavivirus-crossreactive clones recognized dengue-1, -2, -3 and -4 virus, WNV and YFV . We also examined the recognition of purified NS3 proteins of...dengue-l, YFV or WNV Ag. JK44 lysed target cells cultured with dengue-1, -2, and -3, but did not lyse target cells cultured with dengue-4, YFV or WNV Ag

Overview of current situation of dengue and dengue vector control

USDA-ARS?s Scientific Manuscript database

Dengue is the most important arbovirus of humans in the world. It is caused by one of four closely related virus serotypes whose primary vector is Aedes aegypti and secondarily by Ae. albopictus. A global dengue pandemic began in Southeast Asia after World War II and has intensified during the las...

Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials

PubMed Central

Plennevaux, Eric; Moureau, Annick; Arredondo-García, José L; Villar, Luis; Pitisuttithum, Punnee; Tran, Ngoc H; Bonaparte, Matthew; Chansinghakul, Danaya; Coronel, Diana L; L’Azou, Maïna; Ochiai, R Leon; Toh, Myew-Ling; Noriega, Fernando; Bouckenooghe, Alain

2018-01-01

Abstract Background We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. Methods We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2–16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples. Results There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline. Conclusions Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries. Clinical Trials Registration NCT01373281 and NCT01374516. PMID:29300876

Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials.

PubMed

Plennevaux, Eric; Moureau, Annick; Arredondo-García, José L; Villar, Luis; Pitisuttithum, Punnee; Tran, Ngoc H; Bonaparte, Matthew; Chansinghakul, Danaya; Coronel, Diana L; L'Azou, Maïna; Ochiai, R Leon; Toh, Myew-Ling; Noriega, Fernando; Bouckenooghe, Alain

2018-04-03

We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2-16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples. There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline. Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries. NCT01373281 and NCT01374516.

Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

PubMed

Ab-Rahman, Hasliana Azrah; Wong, Pooi-Fong; Rahim, Hafiz; Abd-Jamil, Juraina; Tan, Kim-Kee; Sulaiman, Syuhaida; Lum, Chai-See; Syed-Omar, Syarifah-Faridah; AbuBakar, Sazaly

2015-01-01

HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

DengueME: A Tool for the Modeling and Simulation of Dengue Spatiotemporal Dynamics †

PubMed Central

de Lima, Tiago França Melo; Lana, Raquel Martins; de Senna Carneiro, Tiago Garcia; Codeço, Cláudia Torres; Machado, Gabriel Souza; Ferreira, Lucas Saraiva; de Castro Medeiros, Líliam César; Davis Junior, Clodoveu Augusto

2016-01-01

The prevention and control of dengue are great public health challenges for many countries, particularly since 2015, as other arboviruses have been observed to interact significantly with dengue virus. Different approaches and methodologies have been proposed and discussed by the research community. An important tool widely used is modeling and simulation, which help us to understand epidemic dynamics and create scenarios to support planning and decision making processes. With this aim, we proposed and developed DengueME, a collaborative open source platform to simulate dengue disease and its vector’s dynamics. It supports compartmental and individual-based models, implemented over a GIS database, that represent Aedes aegypti population dynamics, human demography, human mobility, urban landscape and dengue transmission mediated by human and mosquito encounters. A user-friendly graphical interface was developed to facilitate model configuration and data input, and a library of models was developed to support teaching-learning activities. DengueME was applied in study cases and evaluated by specialists. Other improvements will be made in future work, to enhance its extensibility and usability. PMID:27649226

Comparison of real-time SYBR green dengue assay with real-time taqman RT-PCR dengue assay and the conventional nested PCR for diagnosis of primary and secondary dengue infection

PubMed Central

Paudel, Damodar; Jarman, Richard; Limkittikul, Kriengsak; Klungthong, Chonticha; Chamnanchanunt, Supat; Nisalak, Ananda; Gibbons, Robert; Chokejindachai, Watcharee

2011-01-01

Background: Dengue fever and dengue hemorrhagic fever are caused by dengue virus. Dengue infection remains a burning problem of many countries. To diagnose acute dengue in the early phase we improve the low cost, rapid SYBR green real time assay and compared the sensitivity and specificity with real time Taqman® assay and conventional nested PCR assay. Aims: To develop low cost, rapid and reliable real time SYBR green diagnostic dengue assay and compare with Taqman real-time assay and conventional nested PCR (modified Lanciotti). Materials and Methods: Eight cultured virus strains were diluted in tenth dilution down to undetectable level by the PCR to optimize the primer, temperature (annealing, and extension and to detect the limit of detection of the assay. Hundred and ninety three ELISA and PCR proved dengue clinical samples were tested with real time SYBR® Green assay, real time Taqman® assay to compare the sensitivity and specificity. Results: Sensitivity and specificity of real time SYBR® green dengue assay (84% and 66%, respectively) was almost comparable to those (81% and 74%) of Taqman real time PCR dengue assay. Real time SYBR® green RT-PCR was equally sensitive in primary and secondary infection while real time Taqman was less sensitive in the secondary infection. Sensitivity of real time Taqman on DENV3 (87%) was equal to SYBR green real time PCR dengue assay. Conclusion: We developed low cost rapid diagnostic SYBR green dengue assay. Further study is needed to make duplex primer assay for the serotyping of dengue virus. PMID:22363089

Dengue fever outbreak: a clinical management experience.

PubMed

Ahmed, Shahid; Ali, Nadir; Ashraf, Shahzad; Ilyas, Mohammad; Tariq, Waheed-Uz-Zaman; Chotani, Rashid A

2008-01-01

To determine the frequency of dengue as a cause of fever and compare the clinical and haematological characteristics of Dengue-probable and Dengue-proven cases. An observational study. The Combined Military Hospital, Malir Cantt., Karachi, from August 2005 to December 2006. All patients with age above 14 years, who were either hospitalized or treated in medical outdoor clinic due to acute febrile illness, were evaluated for clinical features of Dengue Fever (DF), Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS). Patients showing typical clinical features and haematological findings suggestive of Dengue fever (As per WHO criteria) were evaluated in detail for comparison of probable and confirmed cases of Dengue fever. All other cases of acute febrile illness, not showing clinical features or haematological abnormalities of Dengue fever, were excluded. The clinical and laboratory features were recorded on SPSS 11.0 programme and graded where required, for descriptive and statistical analysis. Out of 5200 patients with febrile illness, 107(2%) presented with typical features of DF, 40/107(37%) were Dengue-proven while 67/107(63%) were Dengue-probable. Out of Dengue-proven cases, 38 were of DF and 2 were of DHF. Day 1 temperature ranged from 99-1050C (mean 1010C). Chills and rigors were noticed in 86 (80%), myalgia in 67%, headache in 54%, pharyngitis in 35%, rash in 28%, and bleeding manifestations in 2% cases. Hepatomegaly in 1(0.5%), lymphadenopathy in 1(0.5%) and splenomegaly in 12 (11.2%) cases. Leucopoenia (count<4x109 /L) was noted in 73%, platelet count<150 x109 /L in 84% and ALT>40 U/L in 57% cases. Frequency of clinically suspected dengue virus infection was 107 (2%), while confirmed dengue fever cases were 40 (0.8%) out of 5200 fever cases. Fever with chills and rigors, body aches, headache, myalgia, rash, haemorrhagic manifestations, platelet count, total leukocyte count, and ALT, are parameters to screen the cases of suspected dengue virus

Economic Cost of Dengue in Puerto Rico

PubMed Central

Halasa, Yara A.; Shepard, Donald S.; Zeng, Wu

2012-01-01

Dengue, endemic in Puerto Rico, reached a record high in 2010. To inform policy makers, we derived annual economic cost. We assessed direct and indirect costs of hospitalized and ambulatory dengue illness in 2010 dollars through surveillance data and interviews with 100 laboratory-confirmed dengue patients treated in 2008–2010. We corrected for underreporting by using setting-specific expansion factors. Work absenteeism because of a dengue episode exceeded the absenteeism for an episode of influenza or acute otitis media. From 2002 to 2010, the aggregate annual cost of dengue illness averaged $38.7 million, of which 70% was for adults (age 15+ years). Hospitalized patients accounted for 63% of the cost of dengue illness, and fatal cases represented an additional 17%. Households funded 48% of dengue illness cost, the government funded 24%, insurance funded 22%, and employers funded 7%. Including dengue surveillance and vector control activities, the overall annual cost of dengue was $46.45 million ($12.47 per capita). PMID:22556069

Dengue 3 Epidemic, Havana, 2001

PubMed Central

Peláez, Otto; Kourí, Gustavo; Pérez, Raúl; San Martín, José L.; Vázquez, Susana; Rosario, Delfina; Mora, Regla; Quintana, Ibrahim; Bisset, Juan; Cancio, Reynel; Masa, Ana M; Castro, Osvaldo; González, Daniel; Avila, Luis C.; Rodríguez, Rosmari; Alvarez, Mayling; Pelegrino, Jose L.; Bernardo, Lídice; Prado, Irina

2004-01-01

In June 2001, dengue transmission was detected in Havana, Cuba; 12,889 cases were reported. Dengue 3, the etiologic agent of the epidemic, caused the dengue hemorrhagic fever only in adults, with 78 cases and 3 deaths. After intensive vector control efforts, no new cases have been detected. PMID:15200868

Dengue antibodies in blood donors.

PubMed

Ribas-Silva, Rejane Cristina; Eid, Andressa Ahmad

2012-01-01

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

Epidemiological Scenario of Dengue in Brazil

PubMed Central

2015-01-01

Dengue is the most important reemerging mosquito-borne viral disease worldwide. It is caused by any of four Dengue virus types or serotypes (DENV-1 to DENV-4) and is transmitted by mosquitoes from the genus Aedes. Ecological changes have favored the geographic expansion of the vector and, since the dengue pandemic in the Asian and Pacific regions, the infection became widely distributed worldwide, reaching Brazil in 1845. The incidence of dengue in Brazil has been frequently high, and the number of cases in the country has at some point in time represented up to 60% of the dengue reported cases worldwide. This review addresses vector distribution, dengue outbreaks, circulating serotypes and genotypes, and prevention approaches being utilized in Brazil. PMID:26413514

Dengue fever among Israeli expatriates in Delhi, 2015: implications for dengue incidence in Delhi, India.

PubMed

Neuberger, Ami; Turgeman, Avigail; Lustig, Yaniv; Schwartz, Eli

2016-03-01

We present the data of 13 dengue cases diagnosed between 1 August and 15 September 2015 among 240 Israeli expatriates residing in Delhi. Attack rates were similar between adults (6/128, 4.7%) and children (7/112, 6.3%). dengue virus (DENV-2) was identified in two and DENV-1 in one dengue-seropositive sample. Another febrile patient was diagnosed with chikungunya virus infection. The reported incidence of dengue fever among people living in Delhi was lower than 0.1% as of September 2015. Based on our results, we hypothesize that the incidence of dengue fever in Delhi is grossly underestimated. © International Society of Travel Medicine, 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dengue Virus Type 3, Brazil, 2002

PubMed Central

Schatzmayr, Hermann Gonçalves; Bispo de Filippis, Ana Maria; Barreto dos Santos, Flávia; Venâncio da Cunha, Rivaldo; Coelho, Janice Oliveira; José de Souza, Luiz; Guimarães, Flávia Ramos; Machado de Araújo, Eliane Saraiva; De Simone, Thatiane Santos; Baran, Meri; Teixeira, Gualberto; Miagostovich, Marize Pereira

2005-01-01

During the summer of 2002, Rio de Janeiro had a large epidemic of dengue fever; 288,245 cases were reported. A subset of 1,831 dengue hemorrhagic fever cases occurred. In this study, performed in the first half of 2002, samples from 1,559 patients with suspected cases of dengue infection were analyzed. From this total, 1,497 were obtained from patients with nonfatal cases, and 62 were obtained from patients with fatal cases. By the use of different methods, 831 (53.3%) cases, including 40 fatal cases, were confirmed as dengue infection. When virus identification was successful, dengue virus type 3 (DENV-3) was obtained in 99% of cases. Neurologic involvement was shown in 1 patient with encephalitis, confirmed by the detection of DENV-3 RNA in the cerebrospinal fluid. This explosive epidemic of DENV-3 was the most severe dengue epidemic reported in Brazil since dengue viruses were introduced in 1986. PMID:16229765

Controversies in dengue pathogenesis

PubMed Central

Halstead, Scott B

2012-01-01

Research into the pathogenesis of dengue fever has exploded over the last half-century, with issues that were considered simple becoming more complex as additional data are found. This has led to the development of a number of controversies that are being studied across the globe and debated in the literature. In this paper, the following six controversies are analysed and, where possible, resolved: the 1997 World Health Organization (WHO) case definition of dengue haemorrhagic fever (DHF) is not useful; DHF is not significantly associated with secondary dengue infection; DHF results from infection with a ‘virulent’ dengue virus; DHF is owing to abnormal T-cell responses; DHF results from auto-immune responses; and DHF results from direct infection of endothelial cells. PMID:22668442

Clinical predictors of dengue fever co-infected with leptospirosis among patients admitted for dengue fever - a pilot study.

PubMed

Suppiah, Jeyanthi; Chan, Shie-Yien; Ng, Min-Wern; Khaw, Yam-Sim; Ching, Siew-Mooi; Mat-Nor, Lailatul Akmar; Ahmad-Najimudin, Naematul Ain; Chee, Hui-Yee

2017-06-28

Dengue and leptospirosis infections are currently two major endemics in Malaysia. Owing to the overlapping clinical symptoms between both the diseases, frequent misdiagnosis and confusion of treatment occurs. As a solution, the present work initiated a pilot study to investigate the incidence related to co-infection of leptospirosis among dengue patients. This enables the identification of more parameters to predict the occurrence of co-infection. Two hundred sixty eight serum specimens collected from patients that were diagnosed for dengue fever were confirmed for dengue virus serotyping by real-time polymerase chain reaction. Clinical, laboratory and demographic data were extracted from the hospital database to identify patients with confirmed leptospirosis infection among the dengue patients. Thus, frequency of co-infection was calculated and association of the dataset with dengue-leptospirosis co-infection was statistically determined. The frequency of dengue co-infection with leptospirosis was 4.1%. Male has higher preponderance of developing the co-infection and end result of shock as clinical symptom is more likely present among co-infected cases. It is also noteworthy that, DENV 1 is the common dengue serotype among all cases identified as dengue-leptospirosis co-infection in this study. The increasing incidence of leptospirosis among dengue infected patients has posed the need to precisely identify the presence of co-infection for the betterment of treatment without mistakenly ruling out either one of them. Thus, anticipating the possible clinical symptoms and laboratory results of dengue-leptospirosis co-infection is essential.

Acute disseminated encephalomyelitis in dengue viral infection.

PubMed

Wan Sulaiman, Wan Aliaa; Inche Mat, Liyana Najwa; Hashim, Hasnur Zaman; Hoo, Fan Kee; Ching, Siew Mooi; Vasudevan, Ramachandran; Mohamed, Mohd Hazmi; Basri, Hamidon

2017-09-01

Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent Advances in Dengue: Relevance to Puerto Rico

PubMed Central

Noyd, David H.; Sharp, Tyler M.

2015-01-01

Dengue represents an increasingly important public health challenge in Puerto Rico, with recent epidemics in 2007, 2010, and 2012–2013. Although recent advances in dengue vaccine development offer hope for primary prevention, the role of health professionals in the diagnosis and management of dengue patients is paramount. Case definitions for dengue, dengue with warning signs, and severe dengue provide a framework to guide clinical decision-making. Furthermore, the differentiation between dengue and other acute febrile illnesses, such as leptospirosis and chikungunya, is necessary for the appropriate diagnosis and management of cases. An understanding of dengue epidemiology and surveillance in Puerto Rico provides context for clinicians in epidemic and non-epidemic periods. This review aims to improve health professionals’ ability to diagnose dengue, and as highlight the relevance of recent advances in dengue prevention and management in Puerto Rico. PMID:26061055

Ferritin levels predict severe dengue.

PubMed

Soundravally, R; Agieshkumar, B; Daisy, M; Sherin, J; Cleetus, C C

2015-02-01

Currently, no tests are available to monitor and predict severity and outcome of dengue. To find potential markers that predict dengue severity, the present study validated the serum level of three acute-phase proteins α-1 antitrypsin, ceruloplasmin and ferritin in a pool of severe dengue cases compared to non-severe forms and other febrile illness controls. A total of 96 patients were divided into two equal groups with group 'A' comprising dengue-infected cases and group 'B' with other febrile illness cases negative for dengue. Out of 48 dengue-infected cases, 13 had severe dengue and the remaining 35 were classified as non-severe dengue. Immunoassays were performed to evaluate the serum levels of acute-phase proteins both on the day of admission and on the day of defervescence. The efficiency of individual proteins in predicting the disease severity was assessed using receiver operating characteristic curve. The study did not find any significant difference in the levels of α-1 antitrypsin between the clinical groups. A significant increase in the levels of ceruloplasmin around defervescence in severe cases compared to non-severe and other febrile controls was observed and this is the first report describing the potential association of ceruloplasmin and dengue severity. Interestingly, a steady increase in the level of serum ferritin was recorded throughout the course of illness. Among all the three proteins, the elevated ferritin level could predict the disease severity with highest sensitivity and specificity of 76.9 and 83.3 %, respectively, on the day of admission and the same was found to be 90 and 91.6 % around defervescence. On the basis of this diagnostic efficiency, we propose that ferritin may serve as a potential biomarker for an early prediction of disease severity.

Dengue in a changing climate.

PubMed

Ebi, Kristie L; Nealon, Joshua

2016-11-01

Dengue is the world's most important arboviral disease in terms of number of people affected. Over the past 50 years, incidence increased 30-fold: there were approximately 390 million infections in 2010. Globalization, trade, travel, demographic trends, and warming temperatures are associated with the recent spread of the primary vectors Aedes aegypti and Aedes albopictus and of dengue. Overall, models project that new geographic areas along the fringe of current geographic ranges for Aedes will become environmentally suitable for the mosquito's lifecycle, and for dengue transmission. Many endemic countries where dengue is likely to spread further have underdeveloped health systems, increasing the substantial challenges of disease prevention and control. Control focuses on management of Aedes, although these efforts have typically had limited effectiveness in preventing outbreaks. New prevention and control efforts are needed to counter the potential consequences of climate change on the geographic range and incidence of dengue, including novel methods of vector control and dengue vaccines. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Dengue viruses – an overview

PubMed Central

Bäck, Anne Tuiskunen; Lundkvist, Åke

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. PMID:24003364

Recent advances in understanding dengue

PubMed Central

Yacoub, Sophie; Mongkolsapaya, Juthathip; Screaton, Gavin

2016-01-01

Dengue is an emerging threat to billions of people worldwide. In the last 20 years, the incidence has increased four-fold and this trend appears to be continuing. Caused by one of four viral serotypes, dengue can present as a wide range of clinical phenotypes with the severe end of the spectrum being defined by a syndrome of capillary leak, coagulopathy, and organ impairment. The pathogenesis of severe disease is thought to be in part immune mediated, but the exact mechanisms remain to be defined. The current treatment of dengue relies on supportive measures with no licensed therapeutics available to date. There have been recent advances in our understanding of a number of areas of dengue research, of which the following will be discussed in this review: the drivers behind the global dengue pandemic, viral structure and epitope binding, risk factors for severe disease and its pathogenesis, as well as the findings of recent clinical trials including therapeutics and vaccines. We conclude with current and future dengue control measures and key areas for future research. PMID:26918159

Serodiagnosis of dengue infection using rapid immunochromatography test in patients with probable dengue infection.

PubMed

Kidwai, Aneela Altaf; Jamal, Qaiser; Saher; Mehrunnisa; Farooqi, Faiz-ur-rehman; Saleem-Ullah

2010-11-01

To determine the frequency of seropositive dengue infection using rapid immunochromatographic assay in patients with probable dengue infection as per WHO criteria. A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immunochromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results.

Sofosbuvir as treatment against dengue?

PubMed

Gan, Chye Sheng; Lim, See Khai; Chee, Chin Fei; Yusof, Rohana; Heh, Choon Han

2018-02-01

Dengvaxia ® (CTD-TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD-TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti-HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS-461203) was predicted to bind to the catalytic motif (Gly-Asp-Asp) of dengue viral polymerase with binding affinity of -6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC 90 of 0.4 μm. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS-461203 to exert its antidengue potential. All in all, sofosbuvir should be subjected to in-depth studies to provide information of its efficacy toward dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue. © 2017 John Wiley & Sons A/S.

Characteristic of dengue disease in Taiwan: 2002-2007.

PubMed

Lin, Chien-Chou; Huang, Yh-Hsiung; Shu, Pei-Yun; Wu, Ho-Sheng; Lin, Yee-Shin; Yeh, Trai-Ming; Liu, Hsiao-Sheng; Liu, Ching-Chuan; Lei, Huan-Yao

2010-04-01

Taiwan's dengue outbreaks have a unique type of transmission: starting by import from abroad in early summer, spreading out locally, and ending in the winter. This pattern repeats every year. Most of the dengue patients are adults, with dengue fever peaking in the 50-54 year age range, and dengue hemorrhagic fever in the 60-64 year age range. Two patterns of dengue infection were found: DENV-2 in 2002 with 74% of secondary infection in contrast to non-DENV-2 (DENV-1 or DENV-3) in 2004-2007 with approximately 70% of primary infection. Secondary dengue virus infection increases disease morbidity, but not mortality in adults. The active serological surveillance shows two-thirds of the dengue-infected adults are symptomatic post infection. The Taiwanese experience of adult dengue should be valuable for countries or areas where, although dengue is not endemic, the Aedes aegypti vector exists and dengue virus can be introduced by travelers.

Dengue in an area of the Colombian Caribbean.

PubMed

Alvis-Guzman, Nelson; Rodríguez-Barreto, Heidi; Mattar-Velilla, Salim

2015-01-01

In Colombia, dengue is an endemic disease and the four serotypes have been reported. To describe the frequency and severity of dengue in an area of the Colombian Caribbean (Department of Cordoba). A retrospective study was conducted. Two data sources were analysed: The database from the Direction of Health in Córdoba, and clinical registers of patients diagnosed with haemorrhagic fevers and fevers of unknown origin in reference hospitals. The mean incidence of dengue between 2003-2010 was 36.5 cases/10(5) inhabitants (CI95%: 34.3-37.5) and adjusted for sub-reporting, could be between 178.5 and 521.6. The mean incidence of severe dengue was 4.7 cases/10(5) inhabitants (CI95%: 4.3-5.0). Mean mortality rate due to dengue was 0.3 cases/10(5) inhabitants. The fatality rate was below 1%. The mean total leukocyte count in patients with dengue was 6,181 mm(3) (CI95%: 5,973-6,389) and with severe Dengue was 4,729 mm(3) (CI95%: 4,220-5,238). The average platelet count in patients with Dengue was 118,793/mm(3) (CI95%: 107,255-130,331) and in patients with Severe Dengue 77,655 (CI95%: 59,640-95,670). Both differences were statistically significant (p <0.05). The frequency of laboratories test per patient in patients with Dengue and severe Dengue were different. The department of Cordoba is a highly endemic zone of Dengue and severe Dengue in the Colombian Caribbean. Moreover, the results show significant differences between dengue and severe dengue so much in tests as in frequency of use of healthcare services.

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.

Simultaneous detection and serotyping of dengue infection using single tube multiplex CDC Dengue Real-Time RT-PCR from India.

PubMed

Sharma, Shashi; Tandel, Kundan; Danwe, Surabhi; Bhatt, Puneet; Dash, P K; Ranjan, Praveer; Rathi, K R; Gupta, Rajiv Mohan; Parida, M M

2018-03-01

Four antigenically different dengue virus serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) are known to cause infections in humans. Some of these are known to cause more severe disease than the others. Chances for developing Dengue hemorrhagic fever-dengue shock syndrome (DHF-DSS) increases significantly with history of previous infection with one of the four serotypes. Therefore, early diagnosis, serotyping and providing early warning of dengue fever epidemics to concerned authorities becomes very important for better patient outcome and to curb the rapid spread in the community. During the 2014 outbreak, a total of 100 samples from suspected cases of dengue were collected. NS1 antigen based rapid test was used for serological diagnosis. Dengue complex one step reverse transcription-polymerase chain reaction was performed to look for presence of viral RNA. Single tube multiplex RT-PCR was also performed to look for infecting serotype. CDC Dengue Multiplex Real Time PCR assay was performed for rapid diagnosis and simultaneous serotyping of the dengue virus. Out of the 100 samples screened, 69 were found to be positive by NS1Ag Rapid test. 34 samples were found positive by dengue consensus RT-PCR assay. 22 samples were found to be positive by single tube Dengue multiplex RT-PCR assay. Serotype DEN-2 was present in maximum numbers followed by DEN-3. 44 samples were found positive by DENV CDC Multiplex Real time PCR assay. DEN-2 was found in maximum numbers followed by DEN-1. Dengue remains to be an important health problem in India and across the globe. Few serotypes of dengue are more dangerous than the others. Rapid diagnosis and serotyping remains the key for better patient management and prevention of disease spreading in the community. Highly sensitive, specific and rapid CDC real time RT-PCR assay was found to be most promising tool among all available molecular diagnostic methods. This will serve a rapid and reliable simultaneous dengue virus detection as well

Application of the dengue virus NS1 antigen rapid test for on-site detection of imported dengue cases at airports.

PubMed

Shu, Pei-Yun; Yang, Cheng-Fen; Kao, Jeng-Fong; Su, Chien-Ling; Chang, Shu-Fen; Lin, Chien-Chou; Yang, Wen-Chih; Shih, Hsiu; Yang, Shih-Yan; Wu, Ping-Fuai; Wu, Ho-Sheng; Huang, Jyh-Hsiung

2009-04-01

We used the dengue virus NS1 antigen (Ag) rapid test for on-site detection of imported dengue cases at airports. Among 22 positive cases of dengue identified from 850 patients with a fever suspected to have dengue, 17 were NS1 Ag test positive. These findings demonstrate the usefulness of the NS1 Ag rapid test in screening imported dengue cases at airports.

Application of the Dengue Virus NS1 Antigen Rapid Test for On-Site Detection of Imported Dengue Cases at Airports▿

PubMed Central

Shu, Pei-Yun; Yang, Cheng-Fen; Kao, Jeng-Fong; Su, Chien-Ling; Chang, Shu-Fen; Lin, Chien-Chou; Yang, Wen-Chih; Shih, Hsiu; Yang, Shih-Yan; Wu, Ping-Fuai; Wu, Ho-Sheng; Huang, Jyh-Hsiung

2009-01-01

We used the dengue virus NS1 antigen (Ag) rapid test for on-site detection of imported dengue cases at airports. Among 22 positive cases of dengue identified from 850 patients with a fever suspected to have dengue, 17 were NS1 Ag test positive. These findings demonstrate the usefulness of the NS1 Ag rapid test in screening imported dengue cases at airports. PMID:19193828

Cost of Dengue Vector Control Activities in Malaysia

PubMed Central

Packierisamy, P. Raviwharmman; Ng, Chiu-Wan; Dahlui, Maznah; Inbaraj, Jonathan; Balan, Venugopalan K.; Halasa, Yara A.; Shepard, Donald S.

2015-01-01

Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently spread rapidly, especially in the tropical countries of the Americas and Asia-Pacific regions. It is endemic in Malaysia, with an annual average of 37,937 reported dengue cases from 2007 to 2012. This study measured the overall economic impact of dengue in Malaysia, and estimated the costs of dengue prevention. In 2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its National Dengue Vector Control Program. This spending represented US$1,591 per reported dengue case and US$2.68 per capita population. Most (92.2%) of this spending occurred in districts, primarily for fogging. A previous paper estimated the annual cost of dengue illness in the country at US$102.2 million. Thus, the inclusion of preventive activities increases the substantial estimated cost of dengue to US$175.7 million, or 72% above illness costs alone. If innovative technologies for dengue vector control prove efficacious, and a dengue vaccine was introduced, substantial existing spending could be rechanneled to fund them. PMID:26416116

[Hepatic alterations in patients with dengue].

PubMed

Larreal, Yraima; Valero, Nereida; Estévez, Jesús; Reyes, Ivette; Maldonado, Mery; Espina, Luz Marina; Arias, Julia; Meleán, Eddy; Añez, German; Atencio, Ricardo

2005-06-01

Clinical features of Dengue are very variable due to multiple alterations induced by the virus in the organism. Increased levels of transaminases similar to those produced by the Hepatitis virus have been reported in patients with Dengue from hiperendemic zones in Asia. The objectives of this study were to determine alterations in the liver tests in patients with Dengue and to relate them to the disease, clinically and serologically. Clinical history, hemathological tests serum transaminases (ALT y AST) and bilirubin assays were performed in 62 patients with clinical and serological diagnosis of Dengue. According to clinical features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of Dengue reffered abdominal pain and 2 patients with DHF had ictericia and hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue and of patients with DHF severe thrombocytopenia (< 50.000 platelets x mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase values five fold higher than the normal values (p < 0.005) were observed in 36.8% and 74.4% of patients with CD and DHF respectively; AST was predominant in both groups. Our results suggest liver damage during the course of Dengue. A differential diagnosis has to be done between the hepatic involvement of Dengue cases and others viral diseases with hepatic disfunctions.

Dengue in Peace Corps Volunteers, 2000-14.

PubMed

Ferguson, Rennie W; Henderson, Susan J; Lee, E Avery; Jung, Paul

2016-03-01

Dengue is an arboviral disease estimated to cause 50-100 million infections each year in >100 tropical and subtropical countries. Urbanization, human population growth and expanded global travel have resulted in an increase in the incidence of dengue worldwide. International travellers to areas with endemic dengue are at risk of contracting dengue and US Peace Corps Volunteers are one specific group of long-term travellers who are exposed to environments where dengue can be contracted. Cases of dengue among Peace Corps Volunteers, defined as clinically apparent infections with laboratory-confirmation by a positive NS1 antigen test, demonstration of IgM antibodies or by a 4-fold increase in IgG antibodies, between 1 January 2000 and 31 December 2014, reported to the Peace Corps’ Epidemiologic Surveillance System were analyzed. Overall there were 1448 cases of dengue reported among Volunteers, with an incidence rate of 1.12 cases per 1000 Volunteer-months (95% CI 1.06-1.17). The highest rate of dengue among Volunteers was reported in the Caribbean region, with a rate of 5.51 cases per 1000 Volunteer-months (95% CI 4.97-6.10), followed by the East Asia/South Asia region (3.34, 95% CI 2.96-3.75) and Central America (2.55, 95% CI 2.32-2.79). The rate of dengue peaked in 2007, 2010 and 2013. Each peak year was followed by a trough year. Globally, there appears to be a 3-year cyclical pattern of dengue incidence among Volunteers, with differences by region. Dengue continues to be a priority health issue for travellers to endemic areas, and enhanced surveillance of dengue among international travellers may result in improved patient education and prevention efforts. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

[Dengue virus serotype 1 (DENV-1) from Colombia: its contribution to dengue occurrence in Santander].

PubMed

Ocazionez-Jiménez, Raquel E; Ortiz-Báez, Ayda Susana; Gómez-Rangel, Sergio Yebrail; Miranda-Esquivel, Daniel R

2013-09-01

Between 1998 and 2008 all dengue virus serotypes circulated in the Departamento de Santander, an endemic region in northeastern Colombia. No information is available as to the role of serotype 1 (DENV-1) with respect to epidemiology of dengue. To analyze the relationship between changes in DENV-1 predominance with respect to genetic diversity, prevalence of others serotypes and occurrence of severe dengue. Virus genetic diversity was studied by phylogenetic analysis comparing E gene sequences from 12 viral strains. Data about serotypes predominance obtained in previous studies and official data about dengue incidence were used for analysis. Selected viruses grouped into genotype V together DENV-1 from Latin America countries, and segregation in four lineages was evidenced. Changes in virus predominance coincided with replacement of lineage, increase in prevalence of DENV-2 and DENV-3 and increase of severe dengue. Genetic divergence could have contributed to changes in DENV-1 predominance. The relationship of the virus with DENV-2 and DENV-3 could create scenarios that promote occurrence of severe cases. More studies are required to ascertain the precise role of serotypes in the epidemiology of dengue.

Myanmar Dengue Outbreak Associated with Displacement of Serotypes 2, 3, and 4 by Dengue 1

PubMed Central

Thu, Hlaing Myat; Lowry, Kym; Myint, Thein Thein; Shwe, Than Nu; Han, Aye Maung; Khin, Kyu Kyu; Thant, Kyaw Zin; Thein, Soe

2004-01-01

In 2001, Myanmar (Burma) had its largest outbreak of dengue—15,361 reported cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), including 192 deaths. That year, 95% of dengue viruses isolated from patients were serotype 1 viruses belonging to two lineages that had diverged from an earlier, now extinct, lineage sometime before 1998. The ratio of DHF to DSS cases in 2001 was not significantly different from that in 2000, when 1,816 cases of DHF/DSS were reported and dengue 1 also was the most frequently isolated serotype. However, the 2001 ratio was significantly higher than that in 1998 (also an outbreak year) and in 1999, when all four serotypes were detected and serotypes 1, 2, and 3 were recovered in similar numbers. The large number of clinical cases in 2001 may have been due, in part, to a preponderance of infections with dengue 1 viruses. PMID:15200847

Dengue fever: a Wikipedia clinical review.

PubMed

Heilman, James M; De Wolff, Jacob; Beards, Graham M; Basden, Brian J

2014-01-01

Dengue fever, also known as breakbone fever, is a mosquito-borne infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into life-threatening dengue hemorrhagic fever, which results in bleeding, thrombocytopenia, and leakage of blood plasma, or into dengue shock syndrome, in which dangerously low blood pressure occurs. Treatment of acute dengue fever is supportive, with either oral or intravenous rehydration for mild or moderate disease and use of intravenous fluids and blood transfusion for more severe cases. Along with attempts to eliminate the mosquito vector, work is ongoing to develop a vaccine and medications targeted directly at the virus.

Cost of Dengue Vector Control Activities in Malaysia.

PubMed

Packierisamy, P Raviwharmman; Ng, Chiu-Wan; Dahlui, Maznah; Inbaraj, Jonathan; Balan, Venugopalan K; Halasa, Yara A; Shepard, Donald S

2015-11-01

Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently spread rapidly, especially in the tropical countries of the Americas and Asia-Pacific regions. It is endemic in Malaysia, with an annual average of 37,937 reported dengue cases from 2007 to 2012. This study measured the overall economic impact of dengue in Malaysia, and estimated the costs of dengue prevention. In 2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its National Dengue Vector Control Program. This spending represented US$1,591 per reported dengue case and US$2.68 per capita population. Most (92.2%) of this spending occurred in districts, primarily for fogging. A previous paper estimated the annual cost of dengue illness in the country at US$102.2 million. Thus, the inclusion of preventive activities increases the substantial estimated cost of dengue to US$175.7 million, or 72% above illness costs alone. If innovative technologies for dengue vector control prove efficacious, and a dengue vaccine was introduced, substantial existing spending could be rechanneled to fund them. © The American Society of Tropical Medicine and Hygiene.

Evaluation of laboratory tests for dengue diagnosis in clinical specimens from consecutive patients with suspected dengue in Belo Horizonte, Brazil.

PubMed

Ferraz, Fernanda Oliveira; Bomfim, Maria Rosa Quaresma; Totola, Antônio Helvécio; Ávila, Thiago Vinícius; Cisalpino, Daniel; Pessanha, José Eduardo Marques; da Glória de Souza, Danielle; Teixeira Júnior, Antônio Lúcio; Nogueira, Maurício Lacerda; Bruna-Romero, Oscar; Teixeira, Mauro Martins

2013-09-01

Dengue is a widely spread arboviral disease in tropical and subtropical regions of the world. Dengue fever presents clinical characteristics similar to other febrile illness. Thus laboratory diagnosis is important for adequate management of the disease. The present study was designed to evaluate the diagnostic performance of real-time PCR and serological methods for dengue in a real epidemic context. Clinical data and blood samples were collected from consecutive patients with suspected dengue who attended a primary health care unit in Belo Horizonte, Brazil. Serologic methods and real-time PCR were performed in serum samples to confirm dengue diagnosis. Among the 181 consecutive patients enrolled in this study with suspected dengue, 146 were considered positive by serological criteria (positive NS1 ELISA and/or anti-dengue IgM ELISA) and 138 were positive by real-time PCR. Clinical criteria were not sufficient for distinguishing between dengue and non-dengue febrile illness. The PCR reaction was pre-optimized using samples from patients with known viral infection. It had similar sensitivity compared to NS1 ELISA (88% and 89%, respectively). We also evaluated three commercial lateral flow immunochromatographic tests for NS1 detection (BIOEASY, BIORAD and PANBIO). All three tests showed high sensitivity (94%, 91% and 81%, respectively) for dengue diagnosis. According to our results it can be suggested that lateral flow tests for NS1 detection are the most feasible methods for early diagnosis of dengue. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Reemergence of Dengue in Southern Texas, 2013.

PubMed

Thomas, Dana L; Santiago, Gilberto A; Abeyta, Roman; Hinojosa, Steven; Torres-Velasquez, Brenda; Adam, Jessica K; Evert, Nicole; Caraballo, Elba; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L; Smith, Brian; Banicki, Alison; Tomashek, Kay M; Gaul, Linda; Sharp, Tyler M

2016-06-01

During a dengue epidemic in northern Mexico, enhanced surveillance identified 53 laboratory-positive cases in southern Texas; 26 (49%) patients acquired the infection locally, and 29 (55%) were hospitalized. Of 83 patient specimens that were initially IgM negative according to ELISA performed at a commercial laboratory, 14 (17%) were dengue virus positive by real-time reverse transcription PCR performed at the Centers for Disease Control and Prevention. Dengue virus types 1 and 3 were identified, and molecular phylogenetic analysis demonstrated close identity with viruses that had recently circulated in Mexico and Central America. Of 51 household members of 22 dengue case-patients who participated in household investigations, 6 (12%) had been recently infected with a dengue virus and reported no recent travel, suggesting intrahousehold transmission. One household member reported having a recent illness consistent with dengue. This outbreak reinforces emergence of dengue in southern Texas, particularly when incidence is high in northern Mexico.

Spatiotemporal Dynamics of Dengue Epidemics, Southern Vietnam

PubMed Central

Cuong, Hoang Quoc; Vu, Nguyen Thanh; Cazelles, Bernard; Boni, Maciej F.; Thai, Khoa T.D.; Rabaa, Maia A.; Quang, Luong Chan; Simmons, Cameron P.; Huu, Tran Ngoc

2013-01-01

An improved understanding of heterogeneities in dengue virus transmission might provide insights into biological and ecologic drivers and facilitate predictions of the magnitude, timing, and location of future dengue epidemics. To investigate dengue dynamics in urban Ho Chi Minh City and neighboring rural provinces in Vietnam, we analyzed a 10-year monthly time series of dengue surveillance data from southern Vietnam. The per capita incidence of dengue was lower in Ho Chi Minh City than in most rural provinces; annual epidemics occurred 1–3 months later in Ho Chi Minh City than elsewhere. The timing and the magnitude of annual epidemics were significantly more correlated in nearby districts than in remote districts, suggesting that local biological and ecologic drivers operate at a scale of 50–100 km. Dengue incidence during the dry season accounted for 63% of variability in epidemic magnitude. These findings can aid the targeting of vector-control interventions and the planning for dengue vaccine implementation. PMID:23735713

Reemergence of Dengue in Southern Texas, 2013

PubMed Central

Thomas, Dana L.; Santiago, Gilberto A.; Abeyta, Roman; Hinojosa, Steven; Torres-Velasquez, Brenda; Adam, Jessica K.; Evert, Nicole; Caraballo, Elba; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L.; Smith, Brian; Banicki, Alison; Tomashek, Kay M.; Gaul, Linda

2016-01-01

During a dengue epidemic in northern Mexico, enhanced surveillance identified 53 laboratory-positive cases in southern Texas; 26 (49%) patients acquired the infection locally, and 29 (55%) were hospitalized. Of 83 patient specimens that were initially IgM negative according to ELISA performed at a commercial laboratory, 14 (17%) were dengue virus positive by real-time reverse transcription PCR performed at the Centers for Disease Control and Prevention. Dengue virus types 1 and 3 were identified, and molecular phylogenetic analysis demonstrated close identity with viruses that had recently circulated in Mexico and Central America. Of 51 household members of 22 dengue case-patients who participated in household investigations, 6 (12%) had been recently infected with a dengue virus and reported no recent travel, suggesting intrahousehold transmission. One household member reported having a recent illness consistent with dengue. This outbreak reinforces emergence of dengue in southern Texas, particularly when incidence is high in northern Mexico. PMID:27191223

Epidemiology of dengue: past, present and future prospects

PubMed Central

Murray, Natasha Evelyn Anne; Quam, Mikkel B; Wilder-Smith, Annelies

2013-01-01

Dengue is currently regarded globally as the most important mosquito-borne viral disease. A history of symptoms compatible with dengue can be traced back to the Chin Dynasty of 265–420 AD. The virus and its vectors have now become widely distributed throughout tropical and subtropical regions of the world, particularly over the last half-century. Significant geographic expansion has been coupled with rapid increases in incident cases, epidemics, and hyperendemicity, leading to the more severe forms of dengue. Transmission of dengue is now present in every World Health Organization (WHO) region of the world and more than 125 countries are known to be dengue endemic. The true impact of dengue globally is difficult to ascertain due to factors such as inadequate disease surveillance, misdiagnosis, and low levels of reporting. Currently available data likely grossly underestimates the social, economic, and disease burden. Estimates of the global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. The expansion of dengue is expected to increase due to factors such as the modern dynamics of climate change, globalization, travel, trade, socioeconomics, settlement and also viral evolution. No vaccine or specific antiviral therapy currently exists to address the growing threat of dengue. Prompt case detection and appropriate clinical management can reduce the mortality from severe dengue. Effective vector control is the mainstay of dengue prevention and control. Surveillance and improved reporting of dengue cases is also essential to gauge the true global situation as indicated in the objectives of the WHO Global Strategy for Dengue Prevention and Control, 2012–2020. More accurate data will inform the prioritization of research, health policy, and financial resources toward reducing this poorly controlled disease. The objective

Epidemiology of dengue: past, present and future prospects.

PubMed

Murray, Natasha Evelyn Anne; Quam, Mikkel B; Wilder-Smith, Annelies

2013-01-01

Dengue is currently regarded globally as the most important mosquito-borne viral disease. A history of symptoms compatible with dengue can be traced back to the Chin Dynasty of 265-420 AD. The virus and its vectors have now become widely distributed throughout tropical and subtropical regions of the world, particularly over the last half-century. Significant geographic expansion has been coupled with rapid increases in incident cases, epidemics, and hyperendemicity, leading to the more severe forms of dengue. Transmission of dengue is now present in every World Health Organization (WHO) region of the world and more than 125 countries are known to be dengue endemic. The true impact of dengue globally is difficult to ascertain due to factors such as inadequate disease surveillance, misdiagnosis, and low levels of reporting. Currently available data likely grossly underestimates the social, economic, and disease burden. Estimates of the global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. The expansion of dengue is expected to increase due to factors such as the modern dynamics of climate change, globalization, travel, trade, socioeconomics, settlement and also viral evolution. No vaccine or specific antiviral therapy currently exists to address the growing threat of dengue. Prompt case detection and appropriate clinical management can reduce the mortality from severe dengue. Effective vector control is the mainstay of dengue prevention and control. Surveillance and improved reporting of dengue cases is also essential to gauge the true global situation as indicated in the objectives of the WHO Global Strategy for Dengue Prevention and Control, 2012-2020. More accurate data will inform the prioritization of research, health policy, and financial resources toward reducing this poorly controlled disease. The objective of

The global economic burden of dengue: a systematic analysis.

PubMed

Shepard, Donald S; Undurraga, Eduardo A; Halasa, Yara A; Stanaway, Jeffrey D

2016-08-01

Dengue is a serious global burden. Unreported and unrecognised apparent dengue virus infections make it difficult to estimate the true extent of dengue and current estimates of the incidence and costs of dengue have substantial uncertainty. Objective, systematic, comparable measures of dengue burden are needed to track health progress, assess the application and financing of emerging preventive and control strategies, and inform health policy. We estimated the global economic burden of dengue by country and super-region (groups of epidemiologically similar countries). We used the latest dengue incidence estimates from the Institute for Health Metrics and Evaluation's Global Burden of Disease Study 2013 and several other data sources to assess the economic burden of symptomatic dengue cases in the 141 countries and territories with active dengue transmission. From the scientific literature and regressions, we estimated cases and costs by setting, including the non-medical setting, for all countries and territories. Our global estimates suggest that in 2013 there were a total of 58·40 million symptomatic dengue virus infections (95% uncertainty interval [95% UI] 24 million-122 million), including 13 586 fatal cases (95% UI 4200-34 700), and that the total annual global cost of dengue illness was US$8·9 billion (95% UI 3·7 billion-19·7 billion). The global distribution of dengue cases is 18% admitted to hospital, 48% ambulatory, and 34% non-medical. The global cost of dengue is substantial and, if control strategies could reduce dengue appreciably, billions of dollars could be saved globally. In estimating dengue costs by country and setting, this study contributes to the needs of policy makers, donors, developers, and researchers for economic assessments of dengue interventions, particularly with the licensure of the first dengue vaccine and promising developments in other technologies. Sanofi Pasteur. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dengue Fever: Causes, Complications, and Vaccine Strategies

PubMed Central

Khanna, Ira

2016-01-01

Dengue is a highly endemic infectious disease of the tropical countries and is rapidly becoming a global burden. It is caused by any of the 4 serotypes of dengue virus and is transmitted within humans through female Aedes mosquitoes. Dengue disease varies from mild fever to severe conditions of dengue hemorrhagic fever and shock syndrome. Globalization, increased air travel, and unplanned urbanization have led to increase in the rate of infection and helped dengue to expand its geographic and demographic distribution. Dengue vaccine development has been a challenging task due to the existence of four antigenically distinct dengue virus serotypes, each capable of eliciting cross-reactive and disease-enhancing antibody response against the remaining three serotypes. Recently, Sanofi Pasteur's chimeric live-attenuated dengue vaccine candidate has been approved in Mexico, Brazil, and Philippines for usage in adults between 9 and 45 years of age. The impact of its limited application to the public health system needs to be evaluated. Simultaneously, the restricted application of this vaccine candidate warrants continued efforts in developing a dengue vaccine candidate which is additionally efficacious for infants and naïve individuals. In this context, alternative strategies of developing a designed vaccine candidate which does not allow production of enhancing antibodies should be explored, as it may expand the umbrella of efficacy to include infants and naïve individuals. PMID:27525287

Real-time forecasts of dengue epidemics

NASA Astrophysics Data System (ADS)

Yamana, T. K.; Shaman, J. L.

2015-12-01

Dengue is a mosquito-borne viral disease prevalent in the tropics and subtropics, with an estimated 2.5 billion people at risk of transmission. In many areas with endemic dengue, disease transmission is seasonal but prone to high inter-annual variability with occasional severe epidemics. Predicting and preparing for periods of higher than average transmission is a significant public health challenge. Here we present a model of dengue transmission and a framework for optimizing model simulations with real-time observational data of dengue cases and environmental variables in order to generate ensemble-based forecasts of the timing and severity of disease outbreaks. The model-inference system is validated using synthetic data and dengue outbreak records. Retrospective forecasts are generated for a number of locations and the accuracy of these forecasts is quantified.

Development of Peptide Vaccines in Dengue.

PubMed

Reginald, Kavita; Chan, Yanqi; Plebanski, Magdalena; Poh, Chit Laa

2017-09-13

Dengue is one of the most important arboviral infection worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. Hence, there is an urgent need to develop an efficient dengue vaccine for this region. Data from different clinical trials indicate that a successful dengue vaccine must elicit both neutralizing antibodies and cell mediated immunity. This can be achieved by designing a multi-epitope peptide vaccine comprising B, CD8+ and CD4+ T cell epitopes. As recognition of T cell epitopes are restricted by human leukocyte antigens (HLA), T cell epitopes which are able to recognize several major HLAs will be preferentially included in the vaccine design. While peptide vaccines are safe, biocompatible and cost-effective, it is poorly immunogenic. Strategies to improve its immunogenicity by the use of long peptides, adjuvants and nanoparticle delivery mechanisms are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Characteristic of Dengue Disease in Taiwan: 2002–2007

PubMed Central

Lin, Chien-Chou; Huang, Yh-Hsiung; Shu, Pei-Yun; Wu, Ho-Sheng; Lin, Yee-Shin; Yeh, Trai-Ming; Liu, Hsiao-Sheng; Liu, Ching-Chuan; Lei, Huan-Yao

2010-01-01

Taiwan's dengue outbreaks have a unique type of transmission: starting by import from abroad in early summer, spreading out locally, and ending in the winter. This pattern repeats every year. Most of the dengue patients are adults, with dengue fever peaking in the 50–54 year age range, and dengue hemorrhagic fever in the 60–64 year age range. Two patterns of dengue infection were found: DENV-2 in 2002 with 74% of secondary infection in contrast to non-DENV-2 (DENV-1 or DENV-3) in 2004–2007 with ~70% of primary infection. Secondary dengue virus infection increases disease morbidity, but not mortality in adults. The active serological surveillance shows two-thirds of the dengue-infected adults are symptomatic post infection. The Taiwanese experience of adult dengue should be valuable for countries or areas where, although dengue is not endemic, the Aedes aegypti vector exists and dengue virus can be introduced by travelers. PMID:20348527

Live attenuated tetravalent dengue vaccine.

PubMed

Bhamarapravati, N; Sutee, Y

2000-05-26

The development of a live attenuated tetravalent dengue vaccine is currently the best strategy to obtain a vaccine against dengue viruses. The Mahidol University group developed candidate live attenuated vaccines by attenuation through serial passages in certified primary cell cultures. Dengue serotype 1, 2 and 4 viruses were developed in primary dog kidney cells, whereas dengue serotype 3 was serially passaged in primary African green monkey kidney cells. Tissue culture passaged strain viruses were subjected to biological marker studies. Candidate vaccines have been tested as monovalent (single virus), bivalent (two viruses), trivalent (three viruses) and tetravalent (all four serotype viruses) vaccines in Thai volunteers. They were found to be safe and immunogenic in both adults and children. The Mahidol live attenuated dengue 2 virus was also tested in American volunteers and resulted in good immune response indistinguishable from those induced in Thai volunteers. The master seeds from the four live attenuated virus strains developed were provided to Pasteur Merieux Connaught of France for production on an industrial scale following good manufacturing practice guidelines.

[Dengue in Panama, 1993].

PubMed

Quiroz, E; Ortega, M; Guzmán, M G; Vázquez, S; Pelegrino, J L; Campos, C; Bayard, V; Vázquez, M; Kourí, G

1997-01-01

Up to 1993, Panama was the only country in Central America where the autochthonous transmission of dengue virus had been detected without experimenting an explosive epidemic despite being reinfected with the Aedes aegypti mosquito since 1985. The characteristics of this first outbreak reported on November 19, 1993, are described in this paper. It is shown that even when there is a Program for the Surveillance and Control of Dengue, which considers low levels of Aedes aegypti infection and a system for the early detection of the virus, the epidemics appear if the community does not take an active part as it happened in 1994, 1995, and 1996. The 14 cases reported were located in an area under the responsibility of the Health Center in San Isidro, Belisario Porras, Special District of San Miguelito, in Panama City (13 cases in 4 blocks of the sector of Santa Librada and 1 case in San Isidro Valley). 3 patients were under 15 and 8 over 36, the other 3 were between 15 and 24.9 were females. The dengue type 2 virus was isolated in 3 patients. The presence of IgM and IgG antibodies to dengue was demonstrated in 11 patients, whereas in 8 over 20 it was observed a secondary type answer. According to the clinical picture, the epidemic was classified as dengue fever. The seroepidemiological survey carried out in the sector of Santa Librada and its surroundings 5 months after the appearance of the symptoms in the first case showed a prevalence of antibodies to dengue of 5.7% (46/802), mainly among individuals over 44. These results confirmed that the outbreak was geographically limited.

Social justice, climate change, and dengue.

PubMed

Chang, Aileen Y; Fuller, Douglas O; Carrasquillo, Olveen; Beier, John C

2014-06-14

Climate change should be viewed fundamentally as an issue of global justice. Understanding the complex interplay of climatic and socioeconomic trends is imperative to protect human health and lessen the burden of diseases such as dengue fever. Dengue fever is rapidly expanding globally. Temperature, rainfall, and frequency of natural disasters, as well as non-climatic trends involving population growth and migration, urbanization, and international trade and travel, are expected to increase the prevalence of mosquito breeding sites, mosquito survival, the speed of mosquito reproduction, the speed of viral incubation, the distribution of dengue virus and its vectors, human migration patterns towards urban areas, and displacement after natural disasters. The burden of dengue disproportionately affects the poor due to increased environmental risk and decreased health care. Mobilization of social institutions is needed to improve the structural inequalities of poverty that predispose the poor to increased dengue fever infection and worse outcomes. This paper reviews the link between dengue and climatic factors as a starting point to developing a comprehensive understanding of how climate change affects dengue risk and how institutions can address the issues of social justice and dengue outbreaks that increasingly affect vulnerable urban populations. Copyright © 2014 Chang, Fuller, Carrasquillo, Beier. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

Metformin Use and Severe Dengue in Diabetic Adults.

PubMed

Htun, Htet Lin; Yeo, Tsin Wen; Tam, Clarence C; Pang, Junxiong; Leo, Yee Sin; Lye, David C

2018-02-20

Diabetes mellitus is a risk factor for severe dengue in adults, but few studies have examined the association between metformin use and disease severity in dengue. In addition to its effect on glucose control, metformin has been associated with pleiotropic properties in preclinical studies. Using a cohort of laboratory-confirmed adult (≥21 years) dengue patients with diabetes mellitus admitted to Tan Tock Seng Hospital, we conducted a retrospective cohort study involving 131 (58.7%) metformin users and 92 (41.3%) non-users. Dengue severity was categorized as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in World Health Organization (WHO) 1997 criteria and severe dengue (SD) in WHO 2009 criteria. Multivariable Poisson regression with robust error variance was used to estimate risk ratio (RR). Compared with non-use, metformin use was associated with a decreased risk of developing severe dengue (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI]: 0.37-0.98, P = 0.04). Additionally, there was an inverse dose-response relationship (aRR = 0.69, 95% CI: 0.49-0.98, P = 0.04) with dengue severity as classified by WHO 2009 criteria. Use of metformin, however, was not associated with dengue severity based on WHO 1997 criteria; and no dose-response relationship was noted. Our results suggest metformin use could attenuate disease severity in dengue-infected diabetes mellitus individuals.

Sentinel surveillance of imported dengue via travellers to Europe 2012 to 2014: TropNet data from the DengueTools Research Initiative

PubMed Central

Neumayr, Andreas; Muñoz, Jose; Schunk, Mirjam; Bottieau, Emmanuel; Cramer, Jakob; Calleri, Guido; López-Vélez, Rogelio; Angheben, Andrea; Zoller, Thomas; Visser, Leo; Serre-Delcor, Núria; Genton, Blaise; Castelli, Francesco; Van Esbroeck, Marjan; Matteelli, Alberto; Rochat, Laurence; Sulleiro, Elena; Kurth, Florian; Gobbi, Federico; Norman, Francesca; Torta, Ilaria; Clerinx, Jan; Poluda, David; Martinez, Miguel; Calvo-Cano, Antonia; Sanchez-Seco, Maria Paz; Wilder-Smith, Annelies; Hatz, Christoph; Franco, Leticia

2017-01-01

We describe the epidemiological pattern and genetic characteristics of 242 acute dengue infections imported to Europe by returning travellers from 2012 to 2014. The overall geographical pattern of imported dengue (South-east Asia > Americas > western Pacific region > Africa) remained stable compared with 1999 to 2010. We isolated the majority of dengue virus genotypes and epidemic lineages causing outbreaks and epidemics in Asia, America and Africa during the study period. Travellers acted as sentinels for four unusual dengue outbreaks (Madeira, 2012–13; Luanda, 2013; Dar es Salaam, 2014; Tokyo, 2014). We were able to characterise dengue viruses imported from regions where currently no virological surveillance data are available. Up to 36% of travellers infected with dengue while travelling returned during the acute phase of the infection (up to 7 days after symptom onset) or became symptomatic after returning to Europe, and 58% of the patients with acute dengue infection were viraemic when seeking medical care. Epidemiological and virological data from dengue-infected international travellers can add an important layer to global surveillance efforts. A considerable number of dengue-infected travellers are viraemic after arrival back home, which poses a risk for dengue introduction and autochthonous transmission in European regions where suitable mosquito vectors are prevalent. PMID:28080959

Fighting the Dengue Virus

PubMed Central

Aadil, Muhammad; Shafqat, Muhammad Nabeel

2017-01-01

The incidence of dengue has been on the upsurge in the last decade. It has affected around one-third of the world's population living in endemic areas. It can be asymptomatic or may present with some specific symptoms. No control measures have proven beneficial to decrease the prevalence of this disease. The emergence of dengue vaccine has been a revolutionary hope in the future of patients affected with this disease. No doubt, this vaccine has its limitations and may do more harm than good, but with correct use, it can prove to be the most beneficial step taken in managing dengue so far. PMID:28652954

Use of a Rapid Test for Diagnosis of Dengue during Suspected Dengue Outbreaks in Resource-Limited Regions

PubMed Central

Sharp, Tyler M.; Lalita, Paul; Tikomaidraubuta, Kini; Cardoso, Yolanda Rebello; Naivalu, Taina; Khan, Aalisha Sahu; Marfel, Maria; Hancock, W. Thane; Tomashek, Kay M.; Margolis, Harold S.

2016-01-01

Dengue is major public health problem, globally. Timely verification of suspected dengue outbreaks allows for public health response, leading to the initiation of appropriate clinical care. Because the clinical presentation of dengue is nonspecific, dengue diagnosis would benefit from a sensitive rapid diagnostic test (RDT). We evaluated the diagnostic performance of an RDT that detects dengue virus (DENV) nonstructural protein 1 (NS1) and anti-DENV IgM during suspected acute febrile illness (AFI) outbreaks in four countries. Real-time reverse transcription-PCR and anti-DENV IgM enzyme-linked immunosorbent assay were used to verify RDT results. Anti-DENV IgM RDT sensitivity and specificity ranged from 55.3 to 91.7% and 85.3 to 98.5%, respectively, and NS1 sensitivity and specificity ranged from 49.7 to 92.9% and 22.2 to 89.0%, respectively. Sensitivity varied by timing of specimen collection and DENV serotype. Combined test results moderately improved the sensitivity. The use of RDTs identified dengue as the cause of AFI outbreaks where reference diagnostic testing was limited or unavailable. PMID:27225409

Case Management of Dengue: Lessons Learned

PubMed Central

Kalayanarooj, Siripen; Srikiatkhachorn, Anon

2017-01-01

Abstract The global burden of dengue and its geographic distribution have increased over the past several decades. The introduction of dengue in new areas has often been accompanied by high case-fatality rates. Drawing on the experience in managing dengue cases at the Queen Sirikit National Institute of Child Health in Bangkok, Thailand, this article provides the authors’ perspectives on key clinical lessons to improve dengue-related outcomes. Parallels between this clinical experience and outcomes reported in randomized controlled trials, results of efforts to disseminate practice recommendations, and suggestions for areas for further research are also discussed. PMID:28403440

Vaccines and immunization strategies for dengue prevention

PubMed Central

Liu, Yang; Liu, Jianying; Cheng, Gong

2016-01-01

Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future. PMID:27436365

The 2006 dengue outbreak in Delhi, India.

PubMed

Sinha, N; Gupta, N; Jhamb, R; Gulati, S; Kulkarni Ajit, V

2008-12-01

Dengue is a worldwide condition spread throughout the tropical and subtropical zones between 30 degrees north and 40 degrees south. It is endemic in South East Asia, the pacific, East and West Africa, the Caribbean and the Americas. Dengue outbreaks are occurring almost every three yearly in Delhi for the last 12 years. The latest outbreak was in the year 2006, which started late in August, peaked in the month of October and lasted till late November. We describe here the clinical, hematological and biochemical data of 70 patients of dengue fever diagnosed as per WHO criteria in Lok Nayak Hospital, New Delhi during this outbreak. Hematological parameters were estimated by automated counter and dengue serology was done by capture ELISA technique. The results displayed widespread effect of dengue fever on hematological and biochemical profile. Some of our patients also had atypical dengue manifestations. These results suggest that dengue fever is a major public health problem which can lead to significant morbidity and can even be fatal at times. All efforts should be made to prevent it.

Immunogenicity of sanofi pasteur tetravalent dengue vaccine.

PubMed

Guy, Bruno

2009-10-01

A candidate tetravalent (TV) dengue vaccine based on the yellow fever (YF) 17D vaccine has been developed by sanofi pasteur. This dengue TV vaccine induced a controlled dendritic cell stimulation in vitro. In clinical trials, Th1 and CD8 responses were induced with an IFN-gamma/TNF-alpha ratio favouring IFN-gamma in both cases, regardless of whether the vaccine recipients were flavivirus naive or not. There was an absence of Th2 response in all cases. The Th1 response was dominated by the D4 serotype in flavivirus naive individuals after initial vaccination but broadened to include all serotypes after second vaccination. This broadened response was also observed after primary dengue TV vaccination in subjects previously administered monovalent live-attenuated dengue 1 and dengue 2 vaccines. Notably, virtually no cross-reactivity between YF 17D and dengue NS3 antigens at the CD8 level was observed. Clinical and pre-clinical results support the favourable immunogenicity and short-term safety of the dengue TV. Future studies will establish the longevity of the vaccine-induced immunity and requirements for boosters.

Epidemic dengue and dengue hemorrhagic fever at the Texas-Mexico border: results of a household-based seroepidemiologic survey, December 2005.

PubMed

Ramos, Mary M; Mohammed, Hamish; Zielinski-Gutierrez, Emily; Hayden, Mary H; Lopez, Jose Luis Robles; Fournier, Marta; Trujillo, Alfredo Rodríguez; Burton, Roy; Brunkard, Joan M; Anaya-Lopez, Luis; Banicki, Allison Abell; Morales, Pablo Kuri; Smith, Brian; Muñoz, Jorge L; Waterman, Stephen H

2008-03-01

A dengue-2 epidemic causing dengue hemorrhagic fever (DHF) occurred in the contiguous border cities of Matamoros, Tamaulipas (Mexico), and Brownsville, TX, in 2005. In December, we conducted a household-based epidemiologic survey to determine the incidence and seroprevalence of dengue infection among Matamoros and Brownsville residents and to identify risk factors associated with infection. Antibodies to dengue were measured in 273 individuals. The estimated incidence of recent dengue infection was 32% and 4% among Matamoros and Brownsville participants, respectively. The estimated prevalence of past dengue infection was 77% and 39% among Matamoros and Brownsville participants, respectively. The Breteau index was 28 in Matamoros and 16 in Brownsville, reflecting an abundant winter population of Aedes mosquitoes. Discarded waste tires and buckets were the two largest categories of infested containers found in both cities. Our results underscore the risk for epidemic dengue and DHF in the Texas-Mexico border region.

Mediational effects of self-efficacy dimensions in the relationship between knowledge of dengue and dengue preventive behaviour with respect to control of dengue outbreaks: a structural equation model of a cross-sectional survey.

PubMed

Isa, Affendi; Loke, Yoon K; Smith, Jane R; Papageorgiou, Alexia; Hunter, Paul R

2013-01-01

Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour. We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ(2) = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963). Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours. To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy.

Comparison of PanBio Dengue Duo Enzyme-Linked Immunosorbent Assay (ELISA) and MRL Dengue Fever Virus Immunoglobulin M Capture ELISA for Diagnosis of Dengue Virus Infections in Southeast Asia

PubMed Central

Cuzzubbo, Andrea J.; Vaughn, David W.; Nisalak, Ananda; Solomon, Tom; Kalayanarooj, Siripen; Aaskov, John; Dung, Nguyen Minh; Devine, Peter L.

1999-01-01

The performances of the MRL dengue fever virus immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA) and the PanBio Dengue Duo IgM capture and IgG capture ELISA were compared. Eighty sera from patients with dengue virus infections, 24 sera from patients with Japanese encephalitis (JE), and 78 sera from patients with nonflavivirus infections, such as malaria, typhoid, leptospirosis, and scrub typhus, were used. The MRL test showed superior sensitivity for dengue virus infections (94 versus 89%), while the PanBio test showed superior specificity for JE (79 versus 25%) and other infections (100 versus 91%). The PanBio ELISA showed better overall performance, as assessed by the sum of sensitivity and specificity (F value). When dengue virus and nonflavivirus infections were compared, F values of 189 and 185 were obtained for the PanBio and MRL tests, respectively, while when dengue virus infections and JE were compared, F values of 168 and 119 were obtained. The results obtained with individual sera in the PanBio and MRL IgM ELISAs showed good correlation, but this analysis revealed that the cutoff value of the MRL test was set well below that of the PanBio test. Comparing the sensitivity and specificity of the tests at different cutoff values (receiver-operator analysis) revealed that the MRL and PanBio IgM ELISAs performed similarly in distinguishing dengue virus from nonflavivirus infections, although the PanBio IgM ELISA showed significantly better distinction between dengue virus infections and JE. The implications of these findings for the laboratory diagnosis of dengue are discussed. PMID:10473522

Preparing for introduction of a dengue vaccine: recommendations from the 1st Dengue v2V Asia-Pacific Meeting.

PubMed

Lam, Sai Kit; Burke, Donald; Capeding, Maria Rosario; Chong, Chee Keong; Coudeville, Laurent; Farrar, Jeremy; Gubler, Duane; Hadinegoro, Sri Rezeki; Hanna, Jeffrey; Lang, Jean; Lee, Han Lim; Leo, Yee Sin; Luong, Chan Quang; Mahoney, Richard; McBride, John; Mendez-Galvan, Jorge; Ng, Lee Ching; Nimmannitya, Suchitra; Ooi, Eng Eong; Shepard, Donald; Smit, Jaco; Teyssou, Rémy; Thomas, Laurent; Torresi, Joseph; Vasconcelos, Pedro; Wirawan, Dewa Nyoman; Yoksan, Sutee

2011-11-28

Infection with dengue virus is a major public health problem in the Asia-Pacific region and throughout tropical and sub-tropical regions of the world. Vaccination represents a major opportunity to control dengue and several candidate vaccines are in development. Experts in dengue and in vaccine introduction gathered for a two day meeting during which they examined the challenges inherent to the introduction of a dengue vaccine into the national immunisation programmes of countries of the Asia-Pacific. The aim was to develop a series of recommendations to reduce the delay between vaccine licensure and vaccine introduction. Major recommendations arising from the meeting included: ascertaining and publicising the full burden and cost of dengue; changing the perception of dengue in non-endemic countries to help generate global support for dengue vaccination; ensuring high quality active surveillance systems and diagnostics; and identifying sustainable sources of funding, both to support vaccine introduction and to maintain the vaccination programme. The attendees at the meeting were in agreement that with the introduction of an effective vaccine, dengue is a disease that could be controlled, and that in order to ensure a vaccine is introduced as rapidly as possible, there is a need to start preparing now. Copyright © 2011 Elsevier Ltd. All rights reserved.

Development of Sanofi Pasteur tetravalent dengue vaccine.

PubMed

Guy, Bruno; Saville, Melanie; Lang, Jean

2010-09-16

The Sanofi Pasteur tetravalent dengue vaccine candidate is composed of 4 recombinant live attenuated vaccines based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the prM and envelope genes of one of the four dengue virus serotypes. Pre-clinical studies have demonstrated that the TV dengue vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than YFV 17D and does not infect mosquitoes by the oral route. In vitro and in vivo preclinical studies also showed that the TV dengue vaccine induced controlled stimulation in human dendritic cells and significant immune responses in monkeys. TV dengue vaccine reactogenicity, viraemia induction and antibody responses were investigated in three Phase I trials in the USA, the Philippines and Mexico, in a two or three-dose regimen over a 12 month period. Results showed that the majority of adverse events were mild to moderate and transient in nature. Viraemia was transient and low, and was not increased after initial dengue TV administration, even in the case of incomplete responses. ϕSeropositivity [≥10 in a PRNT 50 assay] was 100% for all four serotypes in flavivirus-naive adults injected with 3 doses of TV dengue vaccine in the USA. Similarly, seropositivity was 88-100% following three administrations in flavivirus-naive Mexican children aged 2-5 years. Furthermore, the proportion of seropositive subjects increased with each dengue TV injection in the Philippines where baseline flavivirus immunity was high. Responses were also monitored at the cellular level in humans, and their level and nature were in good agreement with the observed safety and the immunogenicity of the vaccine. Finally, the challenges inherent to the development of such TV dengue vaccines will also be discussed in the last part of this review. In conclusion, preclinical and clinical results support the favorable immunogenicity and short-term safety of the dengue TV vaccine. An extensive clinical

Recent progress on sanofi pasteur's dengue vaccine candidate.

PubMed

Lang, Jean

2009-10-01

The sanofi pasteur candidate dengue tetravalent vaccine (TV) is a recombinant live attenuated vaccine. It is based on a backbone of yellow fever vaccine (YF 17D) replication genes and incorporates the envelope genes of the four dengue virus serotypes. Pre-clinical studies have demonstrated that dengue TV is genetically stable, non-hepatotropic, less neurovirulent than YF 17D and does not infect mosquitoes by the oral route. Dengue TV reactogenicity, viraemia induction and antibody responses were investigated in three Phase II trials in the USA, the Philippines and Mexico. Participants were randomised to receive a three-dose regimen of dengue TV over 12 months (given at baseline, 3-4 and 12 months) or a control vaccine/placebo at baseline followed by two injections of dengue TV. Results showed that the majority of adverse events were mild to moderate and transient in nature, while no evidence of induction of viraemia was reported after initial dengue TV administration. Seroconversion was 100% for all four serotypes in flavivirus-naive adults in the USA injected with dengue TV. Similarly, seroconversion was 88-100% following three administrations in flavivirus-naive Mexican children aged 2-5 years. Furthermore, the proportion of seropositive subjects increased with each dengue TV injection in the Philippines where baseline flavivirus immunity was high (80.1%). An extensive clinical development programme for dengue TV is underway including an efficacy trial in Ratchaburi province, Thailand (an area of high dengue incidence). Assuming continued successful outcomes, initial submissions to regulatory authorities are envisaged within a 5-year period.

Dengue vaccine development: strategies and challenges.

PubMed

Ramakrishnan, Lakshmy; Pillai, Madhavan Radhakrishna; Nair, Radhakrishnan R

2015-03-01

Infection with dengue virus may result in dengue fever or a more severe outcome, such as dengue hemorrhagic syndrome/shock. Dengue virus infection poses a threat to endemic regions for four reasons: the presence of four serotypes, each with the ability to cause a similar disease outcome, including fatality; difficulties related to vector control; the lack of specific treatment; and the nonavailability of a suitable vaccine. Vaccine development is considered challenging due to the severity of the disease observed in individuals who have acquired dengue-specific immunity, either passively or actively. Therefore, the presence of vaccine-induced immunity against a particular serotype may prime an individual to severe disease on exposure to dengue virus. Vaccine development strategies include live attenuated vaccines, chimeric, DNA-based, subunit, and inactivated vaccines. Each of the candidates is in various stages of preclinical and clinical development. Issues pertaining to selection pressures, viral interaction, and safety still need to be evaluated in order to induce a complete protective immune response against all four serotypes. This review highlights the various strategies that have been employed in vaccine development, and identifies the obstacles to producing a safe and effective vaccine.

Dengue - Clinical and public health ramifications.

PubMed

Esler, Danielle

2009-11-01

Dengue virus infection is spread by the mosquito vector Aedes aegypti and causes significant morbidity and mortality worldwide. In Australia, it is an important cause of fever in the returned traveller and recent outbreaks have occurred in northern Queensland. A comprehensive understanding of the clinical and public health ramifications of dengue infection is essential for general practitioners. The aim of this article is to review the pathophysiology, clinical manifestations, complications, laboratory investigations and public health consequences of dengue infection. Dengue should be considered as a differential diagnosis of fever in a returned traveller, including in patients who have travelled to northern Queensland within 3 months of an outbreak. Clinical manifestations vary from asymptomatic infection to serious disease. Typical symptoms last 7 days and may include: fever, headache, myalgia, fatigue, abnormal taste sensation, arthralgia, maculopapular rash and anorexia. Around 1% of patients will get the more severe form of the illness, dengue haemorrhagic fever. Recommended diagnostic tests depend on the time since the onset of symptoms. Management involves symptomatic treatment and monitoring for complications. Dengue haemorrhagic fever requires hospitalisation. Prompt notification to public health authorities and advice to patients about prevention of spread are a key role of the GP.

Mediational Effects of Self-Efficacy Dimensions in the Relationship between Knowledge of Dengue and Dengue Preventive Behaviour with Respect to Control of Dengue Outbreaks: A Structural Equation Model of a Cross-Sectional Survey

PubMed Central

Isa, Affendi; Loke, Yoon K.; Smith, Jane R.; Papageorgiou, Alexia; Hunter, Paul R.

2013-01-01

Background Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour. Methods and Findings We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ2 = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963). Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours. Conclusions To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy. PMID:24086777

Current issues in the economics of vaccination against dengue.

PubMed

Tozan, Yesim

2016-01-01

Dengue is a major public health concern in tropical and subtropical areas of the world. The prospects for dengue prevention have recently improved with the results of efficacy trials of a tetravalent dengue vaccine. Although partially effective, once licensed, its introduction can be a public health priority in heavily affected countries because of the perceived public health importance of dengue. This review explores the most immediate economic considerations of introducing a new dengue vaccine and evaluates the published economic analyses of dengue vaccination. Findings indicate that the current economic evidence base is of limited utility to support country-level decisions on dengue vaccine introduction. There are a handful of published cost-effectiveness studies and no country-specific costing studies to project the full resource requirements of dengue vaccine introduction. Country-level analytical expertise in economic analyses, another gap identified, needs to be strengthened to facilitate evidence-based decision-making on dengue vaccine introduction in endemic countries.

Prevalence of dengue virus infection in US travelers who have lived in or traveled to dengue-endemic countries.

PubMed

Sanchez-Vegas, Carolina; Hamer, Davidson H; Chen, Lin H; Wilson, Mary E; Benoit, Christine; Hunsperger, Elizabeth; Macleod, William B; Jentes, Emily S; Ooi, Winnie W; Karchmer, Adolf W; Kogelman, Laura; Yanni, Emad; Marano, Nina; Barnett, Elizabeth D

2013-01-01

Dengue virus (DENV) infections may occur in travelers. To determine prevalence of anti-DENV IgG antibody in travelers who lived in or visited dengue-endemic countries and to describe risk factors and characteristics associated with infection and subsequent anti-DENV IgG antibody presence. Participants were enrolled from travel clinics of the Boston Area Travel Medicine Network from August 2008 through June 2009. Demographic information, trip duration, travel history, and a blood sample were collected. Serum samples were tested for anti-DENV IgG antibody by indirect IgG enzyme-linked immunosorbent assay (ELISA), and antibody-mediated virus neutralization by plaque reduction neutralization test (PRNT) for anti-DENV IgG antibody-positive and selected negative samples. Participants were stratified into group 1: born in dengue-endemic countries; group 2: born in nonendemic countries but lived continuously for ≥1 year in a dengue-endemic country; group 3: born in nonendemic countries and traveled to a dengue-endemic country for ≥2 weeks but <1 year. Six hundred travelers were enrolled. Anti-DENV IgG antibody was identified in 113 (19%) when tested by ELISA (51% in group 1, 40% in group 2, and 6.9% in group 3) and in 71 (12%) by PRNT (42% primary monotypic and 58% heterotypic reactive responses). Sensitivity and specificity of the ELISA based on PRNT results were 85% to 100% and 79% to 94%, assuming up to 15% misclassification of ELISA negative results. Presence of anti-DENV IgG antibody by ELISA was associated with years lived in dengue-endemic countries and birthplace in the Caribbean for group 1, receipt of Japanese encephalitis vaccine in group 3, and self-reported history of dengue in all three groups. Nineteen percent of participants who were born, lived in, or traveled to dengue-endemic countries had anti-DENV IgG antibody by ELISA; 12% had antibodies by PRNT, 85% of whom had no history of dengue. Presence of DENV antibodies was associated with years

Evaluating dengue burden in Africa in passive fever surveillance and seroprevalence studies: protocol of field studies of the Dengue Vaccine Initiative

PubMed Central

Lim, Jacqueline Kyungah; Carabali, Mabel; Lee, Jung-Seok; Lee, Kang-Sung; Namkung, Suk; Lim, Sl-Ki; Ridde, Valéry; Fernandes, Jose; Lell, Bertrand; Matendechero, Sultani Hadley; Esen, Meral; Andia, Esther; Oyembo, Noah; Barro, Ahmed; Bonnet, Emmanuel; Njenga, Sammy M; Agnandji, Selidji Todagbe; Yaro, Seydou; Alexander, Neal; Yoon, In-Kyu

2018-01-01

Introduction Dengue is an important and well-documented public health problem in the Asia-Pacific and Latin American regions. However, in Africa, information on disease burden is limited to case reports and reports of sporadic outbreaks, thus hindering the implementation of public health actions for disease control. To gather evidence on the undocumented burden of dengue in Africa, epidemiological studies with standardised methods were launched in three locations in Africa. Methods and analysis In 2014–2017, the Dengue Vaccine Initiative initiated field studies at three sites in Ouagadougou, Burkina Faso; Lambaréné, Gabon and Mombasa, Kenya to obtain comparable incidence data on dengue and assess its burden through standardised hospital-based surveillance and community-based serological methods. Multidisciplinary measurements of the burden of dengue were obtained through field studies that included passive facility-based fever surveillance, cost-of-illness surveys, serological surveys and healthcare utilisation surveys. All three sites conducted case detection using standardised procedures with uniform laboratory assays to diagnose dengue. Healthcare utilisation surveys were conducted to adjust population denominators in incidence calculations for differing healthcare seeking patterns. The fever surveillance data will allow calculation of age-specific incidence rates and comparison of symptomatic presentation between patients with dengue and non-dengue using multivariable logistic regression. Serological surveys assessed changes in immune status of cohorts of approximately 3000 randomly selected residents at each site at 6-month intervals. The age-stratified serosurvey data will allow calculation of seroprevalence and force of infection of dengue. Cost-of-illness evaluations were conducted among patients with acute dengue by Rapid Diagnostic Test. Ethics and dissemination By standardising methods to evaluate dengue burden across several sites in Africa, these

Use of a Rapid Test for Diagnosis of Dengue during Suspected Dengue Outbreaks in Resource-Limited Regions.

PubMed

Hunsperger, Elizabeth A; Sharp, Tyler M; Lalita, Paul; Tikomaidraubuta, Kini; Cardoso, Yolanda Rebello; Naivalu, Taina; Khan, Aalisha Sahu; Marfel, Maria; Hancock, W Thane; Tomashek, Kay M; Margolis, Harold S

2016-08-01

Dengue is major public health problem, globally. Timely verification of suspected dengue outbreaks allows for public health response, leading to the initiation of appropriate clinical care. Because the clinical presentation of dengue is nonspecific, dengue diagnosis would benefit from a sensitive rapid diagnostic test (RDT). We evaluated the diagnostic performance of an RDT that detects dengue virus (DENV) nonstructural protein 1 (NS1) and anti-DENV IgM during suspected acute febrile illness (AFI) outbreaks in four countries. Real-time reverse transcription-PCR and anti-DENV IgM enzyme-linked immunosorbent assay were used to verify RDT results. Anti-DENV IgM RDT sensitivity and specificity ranged from 55.3 to 91.7% and 85.3 to 98.5%, respectively, and NS1 sensitivity and specificity ranged from 49.7 to 92.9% and 22.2 to 89.0%, respectively. Sensitivity varied by timing of specimen collection and DENV serotype. Combined test results moderately improved the sensitivity. The use of RDTs identified dengue as the cause of AFI outbreaks where reference diagnostic testing was limited or unavailable. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Postmortem Diagnosis of Dengue as an Epidemiological Surveillance Tool

PubMed Central

de Góes Cavalcanti, Luciano Pamplona; Nunes de Melo Braga, Deborah; Maria Alexandre da Silva, Lívia; Gondim Aguiar, Marina; Castiglioni, Mariana; Silva-Junior, José Udevanier; Montenegro de Carvalho Araújo, Fernanda; Allana da Costa Pereira, Renata; Malta, Danielle Lima; Pompeu, Margarida Maria de Lima

2016-01-01

Dengue remains a problem in Brazil, and a substantial number of cases that progress to death are not diagnosed by health services. We evaluated the impact of a protocol adopted by the Coroner's Office Rocha Furtado (CO-RF) for the detection of unreported deaths from dengue in Brazil. We evaluated prospectively cases of deaths referred to the CO-RF with suspicion of dengue and those referred with other diagnosis in which the pathologists suspected dengue as the cause of death. Biological material was collected from all bodies autopsied, for which the suspected cause of death was dengue, between January 2011 and December 2012. Of the 214 bodies autopsied, 134 (62.6%) tested positive for dengue; of these cases, 121 were classified as dengue according to the World Health Organization's case definition (1997 or 2009, as appropriate). Thus, CO-RF detected 90 deaths from dengue, which were not suspected during disease progression. This CO-RF protocol, through a combined effort of the surveillance and laboratory teams, increased the detection of fatal dengue cases by 5-fold. This is the largest series of autopsies performed in cases of death related to dengue in the world to date. PMID:26598561

Peptides as Therapeutic Agents for Dengue Virus

PubMed Central

Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

2017-01-01

Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients. PMID:29200948

An expanded dengue syndrome patient with manifestation myocarditis: case report

NASA Astrophysics Data System (ADS)

Arifijanto, M. V.; Luqmana, H. P.; Rusli, M.; Bramantono

2018-03-01

Dengue infection may manifest asymptomatic, dengue fever, dengue hemorrhagic fever, dengue shock syndrome. However, atypical manifestations in other organs have been increasingly reported and called expanded dengue syndrome. One of the cardiac complications in dengue is myocarditis. An 18-year-old woman complains of high fever since 3 days, epistaxis, chest pain, dyspnea, and vomiting. Laboratory examination obtained thrombocytopenia, hemoconcentration, NS1, IgG-IgM dengue positive, CKMB and Troponin- I increase. Electrocardiogram result ischemic anterior-posterior. Echocardiography results hyperechogenic on myocardial suspicious a myocarditis. The patient was diagnosed with acute myocarditis and dengue hemorrhagic fever. Condition improved after five days of treatment. Cardiac complications in dengue are now increasingly observed with the most common case is myocarditis. The main mechanism of dengue myocarditis is still unknown though both direct viral infection and immune mediated damage have been suggested to be the cause of myocardial damage. The low incidence of dengue myocarditis is because it’s asymptomatic and diagnosis is easily missed. Almost all cases of dengue myocarditis are self-limiting and severe myocarditis leading to dilated cardiomyopathy is extremely rare. There have been reported a patient with dengue hemorrhagic fever with manifestation myocarditis. Condition improve with supportive management.

Clinical profile and outcome of Dengue fever cases.

PubMed

Ratageri, Vinod H; Shepur, T A; Wari, P K; Chavan, S C; Mujahid, I B; Yergolkar, P N

2005-08-01

Dengue fever is on rise globally. In India, Dengue epidemics are expanding geographically, even into the rural areas. Dengue can present with varied manifestations. The mortality rate has been brought down with high index of suspicion, strict monitoring and proper fluid resuscitation. Herewith, we are presenting clinical features and outcome of Dengue cases seen in and around Hubli (North Karnataka).

Dengue score: a proposed diagnostic predictor for pleural effusion and/or ascites in adults with dengue infection.

PubMed

Suwarto, Suhendro; Nainggolan, Leonard; Sinto, Robert; Effendi, Bonita; Ibrahim, Eppy; Suryamin, Maulana; Sasmono, R Tedjo

2016-07-08

There are several limitations in diagnosing plasma leakage using the World Health Organization (WHO) guidelines of dengue hemorrhagic fever. We conducted a study to develop a dengue scoring system to predict pleural effusion and/or ascites using routine laboratory parameters. A prospective observational study was carried out at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Dengue-infected adults admitted on the third febrile day from March, 2010 through August, 2015 were included in the study. A multivariate analysis was conducted to determine the independent diagnostic predictors of pleural effusion and/or ascites and to convert the prediction model into a scoring system. A total of 172 dengue-infected adults were enrolled in the study. Of the 172 patients, 101 (58.7 %) developed pleural effusion and/or ascites. A multivariate analysis was conducted to determine the independent diagnostic predictors of pleural effusion and/or ascites in dengue-infected adults. The predictors were scored based on the following calculations: hemoconcentration ≥15.1 % had a score of 1 (OR, 3.11; 95 % CI, 1.41-6.88), lowest albumin concentration at critical phase ≤3.49 mg/dL had a score of 1 (OR, 4.48; 95 % CI, 1.87-10.77), lowest platelet count ≤49,500/μL had a score of 1 (OR, 3.62; 95 % CI, 1.55-8.49), and elevated ratio of AST ≥2.51 had a score of 1 (OR 2.67; 95 % CI, 1.19-5.97). At a cut off of ≥ 2, the Dengue Score predicted pleural effusion and/or ascites diagnosis with positive predictive value of 79.21 % and negative predictive value of 74.63 %. This prediction model is suitable for calibration and good discrimination. We have developed a Dengue Score that could be used to identify pleural effusion and/or ascites and might be useful to stratify dengue-infected patients at risk for developing severe dengue.

Dengue Infection in Children in Ratchaburi, Thailand: A Cohort Study. I. Epidemiology of Symptomatic Acute Dengue Infection in Children, 2006–2009

PubMed Central

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

2012-01-01

Background There is an urgent need to field test dengue vaccines to determine their role in the control of the disease. Our aims were to study dengue epidemiology and prepare the site for a dengue vaccine efficacy trial. Methods and Findings We performed a prospective cohort study of children in primary schools in central Thailand from 2006 through 2009. We assessed the epidemiology of dengue by active fever surveillance for acute febrile illness as detected by school absenteeism and telephone contact of parents, and dengue diagnostic testing. Dengue accounted for 394 (6.74%) of the 5,842 febrile cases identified in 2882, 3104, 2717 and 2312 student person-years over the four years, respectively. Dengue incidence was 1.77% in 2006, 3.58% in 2007, 5.74% in 2008 and 3.29% in 2009. Mean dengue incidence over the 4 years was 3.6%. Dengue virus (DENV) types were determined in 333 (84.5%) of positive specimens; DENV serotype 1 (DENV-1) was the most common (43%), followed by DENV-2 (29%), DENV-3 (20%) and DENV-4 (8%). Disease severity ranged from dengue hemorrhagic fever (DHF) in 42 (10.5%) cases, dengue fever (DF) in 142 (35.5%) cases and undifferentiated fever (UF) in 210 (52.5%) cases. All four DENV serotypes were involved in all disease severity. A majority of cases had secondary DENV infection, 95% in DHF, 88.7% in DF and 81.9% in UF. Two DHF (0.5%) cases had primary DENV-3 infection. Conclusion The results illustrate the high incidence of dengue with all four DENV serotypes in primary school children, with approximately 50% of disease manifesting as mild clinical symptoms of UF, not meeting the 1997 WHO criteria for dengue. Severe disease (DHF) occurred in one tenth of cases. Data of this type are required for clinical trials to evaluate the efficacy of dengue vaccines in large scale clinical trials. PMID:22860141

Severe Dengue Fever Outbreak in Taiwan

PubMed Central

Wang, Sheng-Fan; Wang, Wen-Hung; Chang, Ko; Chen, Yen-Hsu; Tseng, Sung-Pin; Yen, Chia-Hung; Wu, Deng-Chyang; Chen, Yi-Ming Arthur

2016-01-01

Dengue fever (DF) is a vector-borne disease caused by dengue viruses (DENVs). Epidemic dengue occurs intermittently in Taiwan. In 2014, Taiwan experienced its largest DF outbreak. There were 15,732 DF cases reported. There were a total of 136 dengue hemorrhagic fever (DHF) cases, of which 20 resulted in death. Most DF cases were reported in southern Taiwan. A total of 15,043 (96%) cases were from Kaohsiung, a modern city in southern Taiwan. This report reviews DF epidemics in Taiwan during 2005–2014. The correlation between DF and DHF along with temperature and precipitation were conjointly examined. We conclude that most dengue epidemics in Taiwan resulted from imported DF cases. Results indicate three main factors that may have been associated with this DF outbreak in Kaohsiung: an underground pipeline explosion combined with subsequent rainfall and higher temperature. These factors may have enhanced mosquito breeding activity, facilitating DENV transmission. PMID:26572871

Severe Dengue Fever Outbreak in Taiwan.

PubMed

Wang, Sheng-Fan; Wang, Wen-Hung; Chang, Ko; Chen, Yen-Hsu; Tseng, Sung-Pin; Yen, Chia-Hung; Wu, Deng-Chyang; Chen, Yi-Ming Arthur

2016-01-01

Dengue fever (DF) is a vector-borne disease caused by dengue viruses (DENVs). Epidemic dengue occurs intermittently in Taiwan. In 2014, Taiwan experienced its largest DF outbreak. There were 15,732 DF cases reported. There were a total of 136 dengue hemorrhagic fever (DHF) cases, of which 20 resulted in death. Most DF cases were reported in southern Taiwan. A total of 15,043 (96%) cases were from Kaohsiung, a modern city in southern Taiwan. This report reviews DF epidemics in Taiwan during 2005-2014. The correlation between DF and DHF along with temperature and precipitation were conjointly examined. We conclude that most dengue epidemics in Taiwan resulted from imported DF cases. Results indicate three main factors that may have been associated with this DF outbreak in Kaohsiung: an underground pipeline explosion combined with subsequent rainfall and higher temperature. These factors may have enhanced mosquito breeding activity, facilitating DENV transmission. © The American Society of Tropical Medicine and Hygiene.

Dengue Fever, Hawaii, 2001–2002

PubMed Central

Pang, Lorrin; Kitsutani, Paul; Vorndam, Vance; Nakata, Michele; Ayers, Tracy; Elm, Joe; Tom, Tammy; Reiter, Paul; Rigau-Perez, José G.; Hayes, John M.; Mills, Kristin; Napier, Mike; Clark, Gary G.; Gubler, Duane J.

2005-01-01

Autochthonous dengue infections were last reported in Hawaii in 1944. In September 2001, the Hawaii Department of Health was notified of an unusual febrile illness in a resident with no travel history; dengue fever was confirmed. During the investigation, 1,644 persons with locally acquired denguelike illness were evaluated, and 122 (7%) laboratory-positive dengue infections were identified; dengue virus serotype 1 was isolated from 15 patients. No cases of dengue hemorrhagic fever or shock syndrome were reported. In 3 instances autochthonous infections were linked to a person who reported denguelike illness after travel to French Polynesia. Phylogenetic analyses showed the Hawaiian isolates were closely associated with contemporaneous isolates from Tahiti. Aedes albopictus was present in all communities surveyed on Oahu, Maui, Molokai, and Kauai; no Ae. aegypti were found. This outbreak underscores the importance of maintaining surveillance and control of potential disease vectors even in the absence of an imminent disease threat. PMID:15890132

Dengue in the Americas and Southeast Asia: do they differ?

PubMed

Halstead, Scott B

2006-12-01

The populations of Southeast Asia (SE Asia) and tropical America are similar, and all four dengue viruses of Asian origin are endemic in both regions. Yet, during comparable 5-year periods, SE Asia experienced 1.16 million cases of dengue hemorrhagic fever (DHF), principally in children, whereas in the Americas there were 2.8 million dengue fever (DF) cases, principally in adults, and only 65,000 DHF cases. This review aims to explain these regional differences. In SE Asia, World War II amplified Aedes aegypti populations and the spread of dengue viruses. In the Americas, efforts to eradicate A. aegypti in the 1940s and 1950s contained dengue epidemics mainly to the Caribbean Basin. Cuba escaped infections with the American genotype dengue-2 and an Asian dengue-3 endemic in the 1960s and 1970s. Successive infections with dengue-1 and an Asian genotype dengue-2 resulted in the 1981 DHF epidemic. When this dengue-2 virus was introduced in other Caribbean countries, it encountered populations highly immune to the American genotype dengue-2. During the 1980s and 1990s, rapidly expanding populations of A. aegypti in Brazil permitted successive epidemics of dengue-1, -2, and -3. These exposures, however, resulted mainly in DF, with surprisingly few cases of DHF. The absence of high rates of severe dengue disease in Brazil, as elsewhere in the Americas, may be partly explained by the widespread prevalence of human dengue resistance genes. Understanding the nature and distribution of these genes holds promise for containing severe dengue. Future research on dengue infections should emphasize population-based designs.

Environmentally-driven ensemble forecasts of dengue fever

NASA Astrophysics Data System (ADS)

Yamana, T. K.; Shaman, J. L.

2017-12-01

Dengue fever is a mosquito-borne viral disease prevalent in the tropics and subtropics, with an estimated 2.5 billion people at risk of transmission. In many areas where dengue is found, disease transmission is seasonal but prone to high inter-annual variability with occasional severe epidemics. Predicting and preparing for periods of higher than average transmission remains a significant public health challenge. Recently, we developed a framework for forecasting dengue incidence using an dynamical model of disease transmission coupled with observational data of dengue cases using data-assimilation methods. Here, we investigate the use of environmental data to drive the disease transmission model. We produce retrospective forecasts of the timing and severity of dengue outbreaks, and quantify forecast predictive accuracy.

System Dynamics based Dengue modeling environment to simulate evolution of Dengue infection under different climate scenarios

NASA Astrophysics Data System (ADS)

Anwar, R.; Khan, R.; Usmani, M.; Colwell, R. R.; Jutla, A.

2017-12-01

Vector borne infectious diseases such as Dengue, Zika and Chikungunya remain a public health threat. An estimate of the World Health Organization (WHO) suggests that about 2.5 billion people, representing ca. 40% of human population,are at increased risk of dengue; with more than 100 million infection cases every year. Vector-borne infections cannot be eradicated since disease causing pathogens survive in the environment. Over the last few decades dengue infection has been reported in more than 100 countries and is expanding geographically. Female Ae. Aegypti mosquito, the daytime active and a major vector for dengue virus, is associated with urban population density and regional climatic processes. However, mathematical quantification of relationships on abundance of vectors and climatic processes remain a challenge, particularly in regions where such data are not routinely collected. Here, using system dynamics based feedback mechanism, an algorithm integrating knowledge from entomological, meteorological and epidemiological processes is developed that has potential to provide ensemble simulations on risk of occurrence of dengue infection in human population. Using dataset from satellite remote sensing, the algorithm was calibrated and validated using actual dengue case data of Iquitos, Peru. We will show results on model capabilities in capturing initiation and peak in the observed time series. In addition, results from several simulation scenarios under different climatic conditions will be discussed.

Dengue mortality in Colombia, 1985-2012.

PubMed

Chaparro-Narváez, Pablo; León-Quevedo, Willian; Castañeda-Orjuela, Carlos Andrés

2016-02-11

Dengue in Colombia is an important public health problem due to the huge economic and social costs it has caused, especially during the disease outbreaks.  To describe the behavior of dengue mortality in Colombia between 1985 and 2012.  We conducted a descriptive study. Information was obtained from mortality and population projection databases provided by the Departamento Administrativo Nacional de Estadística (DANE) for the 1985-2012 period. Mortality rates, rate ratios, and case fatality rates were estimated.  A total of 1,990 dengue deaths were registered during this period in Colombia. Dengue mortality rates presented an increasing trend with statistical significance between 1985 and 1998. Higher mortality rates were reported in men both younger than 5 years and older than 65 years. Between 1995 and 2012, category 1 to 4 municipalities reported the highest mortality rates. Case fatality rates varied during the period between 0.01% and 0.39%.  Dengue is an avoidable disease that should disappear from mortality statistics as a cause of death. The event is avoidable if the proposed activities from the Estrategia de Gestión Integrada (EGI)-Dengue are implemented and evaluated. We recommend encouraging the development of an informational culture to contribute to decision making and prioritizing resource allocation.

Costs of dengue prevention and incremental cost of dengue outbreak control in Guantanamo, Cuba.

PubMed

Baly, Alberto; Toledo, Maria E; Rodriguez, Karina; Benitez, Juan R; Rodriguez, Maritza; Boelaert, Marleen; Vanlerberghe, Veerle; Van der Stuyft, Patrick

2012-01-01

To assess the economic cost of routine Aedes aegypti control in an at-risk environment without dengue endemicity and the incremental costs incurred during a sporadic outbreak. The study was conducted in 2006 in the city of Guantanamo, Cuba. We took a societal perspective to calculate costs in months without dengue transmission (January-July) and during an outbreak (August-December). Data sources were bookkeeping records, direct observations and interviews. The total economic cost per inhabitant (p.i.) per month. (p.m.) increased from 2.76 USD in months without dengue transmission to 6.05 USD during an outbreak. In months without transmission, the routine Aedes control programme cost 1.67 USD p.i. p.m. Incremental costs during the outbreak were mainly incurred by the population and the primary/secondary level of the healthcare system, hardly by the vector control programme (1.64, 1.44 and 0.21 UDS increment p.i. p.m., respectively). The total cost for managing a hospitalized suspected dengue case was 296.60 USD (62.0% direct medical, 9.0% direct non-medical and 29.0% indirect costs). In both periods, the main cost drivers for the Aedes control programme, the healthcare system and the community were the value of personnel and volunteer time or productivity losses. Intensive efforts to keep A. aegypti infestation low entail important economic costs for society. When a dengue outbreak does occur eventually, costs increase sharply. In-depth studies should assess which mix of activities and actors could maximize the effectiveness and cost-effectiveness of routine Aedes control and dengue prevention. © 2011 Blackwell Publishing Ltd.

Factors Affecting Dengue Prevention Practices: Nationwide Survey of the Malaysian Public

PubMed Central

Wong, Li Ping; Shakir, Sharina Mahavera Mohamad; Atefi, Narges; AbuBakar, Sazaly

2015-01-01

Background Efforts to stamp dengue in many dengue endemic countries has met little success. There is a need to re-examine and understand how the public at large view the dengue prevention efforts. This study aimed to examine the demographic factors, theoretical constructs of the Health Belief Model and knowledge about dengue and how these influence the practice of dengue prevention. Methods A national telephone survey was carried out with 2,512 individuals of the Malaysian public aged 18–60 years. Results The majority (73%) of the Malaysian public had a total dengue prevention score of 51–100 (of a possible score of 1–100). Multivariate analysis suggests significant correlates of higher dengue prevention practices with demographic background, perception of susceptibility to dengue, perceived density of mosquitoes in the neighbourhood and knowledge about dengue. Households of lower income of which the majority (40.7%) were from the rural areas, were associated with the highest odds [OR = 1.33; 95%CI = 1.09–1.67; p = 0.004] of dengue prevention. Dengue prevention practices were also less likely to be undertaken in neighbourhoods where the responders perceived there is no and/or low density of mosquitoes. Dengue prevention practices are also less likely to be practiced by skilled workers [OR = 0.78; 95%CI = 0.63–0.95; p = 0.029] compared to those unemployed. Higher perceived susceptibility to dengue was associated with higher dengue prevention practices and participants with higher dengue knowledge were found to have a higher level of involvement in dengue prevention practices. Conclusion Results from the study suggest that in formulating approaches to contain dengue, strategies should be developed to cultivate dengue prevention practices among urban population and target areas with low density of mosquitoes where public perceived a less likely chance of getting dengue. Dengue prevention campaigns should focus on messages highlighting the risk of contracting

Developing a Time Series Predictive Model for Dengue in Zhongshan, China Based on Weather and Guangzhou Dengue Surveillance Data.

PubMed

Zhang, Yingtao; Wang, Tao; Liu, Kangkang; Xia, Yao; Lu, Yi; Jing, Qinlong; Yang, Zhicong; Hu, Wenbiao; Lu, Jiahai

2016-02-01

Dengue is a re-emerging infectious disease of humans, rapidly growing from endemic areas to dengue-free regions due to favorable conditions. In recent decades, Guangzhou has again suffered from several big outbreaks of dengue; as have its neighboring cities. This study aims to examine the impact of dengue epidemics in Guangzhou, China, and to develop a predictive model for Zhongshan based on local weather conditions and Guangzhou dengue surveillance information. We obtained weekly dengue case data from 1st January, 2005 to 31st December, 2014 for Guangzhou and Zhongshan city from the Chinese National Disease Surveillance Reporting System. Meteorological data was collected from the Zhongshan Weather Bureau and demographic data was collected from the Zhongshan Statistical Bureau. A negative binomial regression model with a log link function was used to analyze the relationship between weekly dengue cases in Guangzhou and Zhongshan, controlling for meteorological factors. Cross-correlation functions were applied to identify the time lags of the effect of each weather factor on weekly dengue cases. Models were validated using receiver operating characteristic (ROC) curves and k-fold cross-validation. Our results showed that weekly dengue cases in Zhongshan were significantly associated with dengue cases in Guangzhou after the treatment of a 5 weeks prior moving average (Relative Risk (RR) = 2.016, 95% Confidence Interval (CI): 1.845-2.203), controlling for weather factors including minimum temperature, relative humidity, and rainfall. ROC curve analysis indicated our forecasting model performed well at different prediction thresholds, with 0.969 area under the receiver operating characteristic curve (AUC) for a threshold of 3 cases per week, 0.957 AUC for a threshold of 2 cases per week, and 0.938 AUC for a threshold of 1 case per week. Models established during k-fold cross-validation also had considerable AUC (average 0.938-0.967). The sensitivity and specificity

Current Status of Dengue Therapeutics Research and Development

PubMed Central

Ooi, Eng Eong; Vasudevan, Subhash G.

2017-01-01

Abstract Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. PMID:28403438

Two cases of dengue meningitis: a rare first presentation.

PubMed

Goswami, Rudra Prosad; Mukherjee, Arindam; Biswas, Tapan; Karmakar, Partha Sarathi; Ghosh, Alakendu

2012-02-13

Dengue, a mosquito-borne disease caused by a flavivirus, is recognized in over 120 countries with 3.6 billion people living in areas at risk. Neurological manifestations are infrequently reported as clinical consequences of dengue infection. Though severe dengue may be associated with meningoencephalitis, meningitis is a rare initial presentation of otherwise uncomplicated dengue fever. We report two adult patients who presented with fever, headache, and nuchal rigidity without the typical symptoms of dengue infection. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis in one and slight neutrophilic pleocytosis in the other with a normal glucose value and negative bacterial cultures. Dengue was suspected because thrombocytopenia was symptomatic in one patient and documented during the hospital course, and was confirmed by demonstration of IgM antibody in the cerebrospinal fluid samples specific for dengue in both cases. Our report demonstrates that meningitis with or without encephalitis can be the first manifestation of dengue infection. In endemic areas, dengue infection should be considered as a probable etiological agent of meningitis. Regular monitoring of platelet count can be an invaluable diagnostic screening tool. In appropriate clinical settings detection of anti-dengue IgM both in serum and in CSF may lead to correct diagnosis.

Dengue: Knowledge gaps, unmet needs and research priorities

PubMed Central

Katzelnick, Leah C.; Coloma, Josefina; Harris, Eva

2018-01-01

Summary Dengue virus (DENV) is a mosquito-borne pathogen that causes up to ~100 million dengue cases each year, placing a major public health, social and economic burden on numerous low- and middle-income countries (LMICs). Major advances by scientists, vaccine developers, and affected communities are revealing new insights and enabling novel interventions and approaches to dengue prevention and control. Such research has highlighted further questions about both the basic understanding of dengue and efforts to develop new tools. We discuss existing approaches to dengue diagnostics, disease prognosis, surveillance, and vector control in LMICs as well as potential consequences of vaccine introduction. We also summarize current knowledge and recent insights into dengue epidemiology, immunology, and pathogenesis, and their implications for understanding natural infection and current and future vaccines. PMID:28185868

Characterization of the 2013 dengue epidemic in Myanmar with dengue virus 1 as the dominant serotype.

PubMed

Ngwe Tun, Mya Myat; Kyaw, Aung Kyaw; Makki, Nader; Muthugala, Rohitha; Nabeshima, Takeshi; Inoue, Shingo; Hayasaka, Daisuke; Moi, Meng Ling; Buerano, Corazon C; Thwe, Saw Myat; Thant, Kyaw Zin; Morita, Kouichi

2016-09-01

In 2013 in Myanmar, dengue epidemic occurred with 20,255 cases including 84 deaths. This study aimed to determine the serological and molecular characteristics of dengue virus (DENV) infection among children with clinical diagnosis of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) during this period. Single acute serum samples were collected from 300 children in Mandalay Children Hospital, Mandalay, Myanmar. Out of the 300 children, 175 (58.3%) and 183 (61%) were positive for anti-dengue IgM and anti-dengue IgG, respectively. Among the IgM positives, 41 (23.4%) had primary DENV infection. Thirty-nine DENV strains (23 DENV-1, 10 DENV-2 and 6 DENV-4) were successfully isolated after inoculation of the patient serum samples onto C6/36 cells. DENV 1 was the dominant serotype in the 2013 epidemic. There was no correlation between the infecting serotypes and clinical severities. The DENV-1 strains belonged to three lineages of the genotype 1; the DENV-2 strains were of the Asian I genotype and were separated into two lineages; and DENV-4 strains belonged to the same lineage of genotype I. It is of interest to note the diversity of DENV-1 and -2 circulating in the same location during June-August 2013. These DENV isolates were genetically close (98%-100%) to the other previously reported isolates from Myanmar and its neighboring countries, namely China, Thailand, Sri Lanka, Cambodia and Vietnam. Primary DENV infection was still high among the severe dengue cases. Different serotypes of DENV were co-circulating in 2013, however, genotype shift was not observed. Additionally, amino acid mutations were detected in the study strains not seen in the previously reported strains from other countries and Myanmar. This paper provided information on the circulating serotypes for the last 15years and the recent dengue situation in Mandalay, Myanmar after 2006. Copyright © 2016 Elsevier B.V. All rights reserved.

Micronutrients and Dengue

PubMed Central

Ahmed, Sundus; Finkelstein, Julia L.; Stewart, Anna M.; Kenneth, John; Polhemus, Mark E.; Endy, Timothy P.; Cardenas, Washington; Mehta, Saurabh

2014-01-01

Dengue virus infection is the most widespread mosquito-borne viral infection in humans and has emerged as a serious global health challenge. In the absence of effective treatment and vaccine, host factors including nutritional status, which may alter disease progression, need investigation. The interplay between nutrition and other infections is well-established, and modulation of nutritional status often presents a simple low-cost method of interrupting transmission, reducing susceptibility, and/or ameliorating disease severity. This review examines the evidence on the role of micronutrients in dengue virus infection. We found critical issues and often inconsistent results across studies; this finding along with the lack of sufficient literature in this field have limited our ability to make any recommendations. However, vitamins D and E have shown promise in small supplementation trials. In summary, the role of micronutrients in dengue virus infection is an exciting research area and needs to be examined in well-designed studies with larger samples. PMID:25200269

Dengue prediction by the web: Tweets are a useful tool for estimating and forecasting Dengue at country and city level

PubMed Central

Degener, Carolin Marlen; Vinhal, Livia; Coelho, Giovanini; Meira, Wagner; Codeço, Claudia Torres; Teixeira, Mauro Martins

2017-01-01

Background Infectious diseases are a leading threat to public health. Accurate and timely monitoring of disease risk and progress can reduce their impact. Mentioning a disease in social networks is correlated with physician visits by patients, and can be used to estimate disease activity. Dengue is the fastest growing mosquito-borne viral disease, with an estimated annual incidence of 390 million infections, of which 96 million manifest clinically. Dengue burden is likely to increase in the future owing to trends toward increased urbanization, scarce water supplies and, possibly, environmental change. The epidemiological dynamic of Dengue is complex and difficult to predict, partly due to costly and slow surveillance systems. Methodology / Principal findings In this study, we aimed to quantitatively assess the usefulness of data acquired by Twitter for the early detection and monitoring of Dengue epidemics, both at country and city level at a weekly basis. Here, we evaluated and demonstrated the potential of tweets modeling for Dengue estimation and forecast, in comparison with other available web-based data, Google Trends and Wikipedia access logs. Also, we studied the factors that might influence the goodness-of-fit of the model. We built a simple model based on tweets that was able to ‘nowcast’, i.e. estimate disease numbers in the same week, but also ‘forecast’ disease in future weeks. At the country level, tweets are strongly associated with Dengue cases, and can estimate present and future Dengue cases until 8 weeks in advance. At city level, tweets are also useful for estimating Dengue activity. Our model can be applied successfully to small and less developed cities, suggesting a robust construction, even though it may be influenced by the incidence of the disease, the activity of Twitter locally, and social factors, including human development index and internet access. Conclusions Tweets association with Dengue cases is valuable to assist

Dengue prediction by the web: Tweets are a useful tool for estimating and forecasting Dengue at country and city level.

PubMed

Marques-Toledo, Cecilia de Almeida; Degener, Carolin Marlen; Vinhal, Livia; Coelho, Giovanini; Meira, Wagner; Codeço, Claudia Torres; Teixeira, Mauro Martins

2017-07-01

Infectious diseases are a leading threat to public health. Accurate and timely monitoring of disease risk and progress can reduce their impact. Mentioning a disease in social networks is correlated with physician visits by patients, and can be used to estimate disease activity. Dengue is the fastest growing mosquito-borne viral disease, with an estimated annual incidence of 390 million infections, of which 96 million manifest clinically. Dengue burden is likely to increase in the future owing to trends toward increased urbanization, scarce water supplies and, possibly, environmental change. The epidemiological dynamic of Dengue is complex and difficult to predict, partly due to costly and slow surveillance systems. In this study, we aimed to quantitatively assess the usefulness of data acquired by Twitter for the early detection and monitoring of Dengue epidemics, both at country and city level at a weekly basis. Here, we evaluated and demonstrated the potential of tweets modeling for Dengue estimation and forecast, in comparison with other available web-based data, Google Trends and Wikipedia access logs. Also, we studied the factors that might influence the goodness-of-fit of the model. We built a simple model based on tweets that was able to 'nowcast', i.e. estimate disease numbers in the same week, but also 'forecast' disease in future weeks. At the country level, tweets are strongly associated with Dengue cases, and can estimate present and future Dengue cases until 8 weeks in advance. At city level, tweets are also useful for estimating Dengue activity. Our model can be applied successfully to small and less developed cities, suggesting a robust construction, even though it may be influenced by the incidence of the disease, the activity of Twitter locally, and social factors, including human development index and internet access. Tweets association with Dengue cases is valuable to assist traditional Dengue surveillance at real-time and low-cost. Tweets are

Dengue Outbreak in Hadramout, Yemen, 2010: An Epidemiological Perspective

PubMed Central

Ghouth, Abdulla Salim Bin; Amarasinghe, Ananda; Letson, G. William

2012-01-01

We analyzed surveillance data of a dengue outbreak (2010) reported to the Hadramout Health Office (Yemen) and retrospectively analyzed dengue-related epidemiological and entomological events reported in Hadramout from 2005 to 2009. A total of 630 immunoglobulin M (IgM) -confirmed dengue cases of 982 febrile cases was reported during the period from February to June of 2010; 12 cases died, giving case fatality a rate of 1.9%. Among febrile cases, the highest proportion of dengue cases (37.3%) was reported in the 15- to 24-year-old age group. The overall attack rate was 0.89/1,000. The average number of cases reported by month over the preceding 5-year period compared with the 2010 data is consistent with endemicity of dengue in the region and supports epidemic designation for the dengue activity in 2010. Recognition of endemic dengue transmission and potential for substantial dengue epidemics highlight the need for consistent laboratory-based surveillance that can support prevention and control activities accordingly. PMID:22665621

Research on Climate and Dengue in Malaysia: A Systematic Review.

PubMed

Hii, Yien Ling; Zaki, Rafdzah Ahmad; Aghamohammadi, Nasrin; Rocklöv, Joacim

2016-03-01

Dengue is a climate-sensitive infectious disease. Climate-based dengue early warning may be a simple, low-cost, and effective tool for enhancing surveillance and control. Scientific studies on climate and dengue in local context form the basis for advancing the development of a climate-based early warning system. This study aims to review the current status of scientific studies in climate and dengue and the prospect or challenges of such research on a climate-based dengue early warning system in a dengue-endemic country, taking Malaysia as a case study. We reviewed the relationship between climate and dengue derived from statistical modeling, laboratory tests, and field studies. We searched electronic databases including PubMed, Scopus, EBSCO (MEDLINE), Web of Science, and the World Health Organization publications, and assessed climate factors and their influence on dengue cases, mosquitoes, and virus and recent development in the field of climate and dengue. Few studies in Malaysia have emphasized the relationship between climate and dengue. Climatic factors such as temperature, rainfall, and humidity are associated with dengue; however, these relationships were not consistent. Climate change projections for Malaysia show a mounting risk for dengue in the future. Scientific studies on climate and dengue enhance dengue surveillance in the long run. It is essential for institutions in Malaysia to promote research on climate and vector-borne diseases to advance the development of climate-based early warning systems. Together, effective strategies that improve existing research capacity, maximize the use of limited resources, and promote local-international partnership are crucial for sustaining research on climate and health.

Dengue-Associated Posterior Reversible Encephalopathy Syndrome, Vietnam

PubMed Central

Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Nghia, Ho Dang Trung; Phuong, Tran My; Duc, Du Trong; Chau, Nguyen Van Vinh; Wills, Bridget; Lim, Choie Cheio Tchoyoson; Thwaites, Guy; Simmons, Cameron Paul

2018-01-01

Dengue can cause neurologic complications in addition to the more common manifestations of plasma leakage and coagulopathy. Posterior reversible encephalopathy syndrome has rarely been described in dengue, although the pathophysiology of endothelial dysfunction likely underlies both. We describe a case of dengue-associated posterior reversible encephalopathy syndrome and discuss diagnosis and management. PMID:29350156

Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

PubMed

Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

2016-06-01

Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice

PubMed Central

Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

2016-01-01

Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

Case Management of Dengue: Lessons Learned.

PubMed

Kalayanarooj, Siripen; Rothman, Alan L; Srikiatkhachorn, Anon

2017-03-01

The global burden of dengue and its geographic distribution have increased over the past several decades. The introduction of dengue in new areas has often been accompanied by high case-fatality rates. Drawing on the experience in managing dengue cases at the Queen Sirikit National Institute of Child Health in Bangkok, Thailand, this article provides the authors' perspectives on key clinical lessons to improve dengue-related outcomes. Parallels between this clinical experience and outcomes reported in randomized controlled trials, results of efforts to disseminate practice recommendations, and suggestions for areas for further research are also discussed. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The Nicaraguan Pediatric Dengue Cohort Study: Incidence of Inapparent and Symptomatic Dengue Virus Infections, 2004–2010

PubMed Central

Gordon, Aubree; Kuan, Guillermina; Mercado, Juan Carlos; Gresh, Lionel; Avilés, William; Balmaseda, Angel; Harris, Eva

2013-01-01

Dengue, caused by the four serotypes of dengue virus (DENV), is the most prevalent mosquito-borne viral disease of humans. To examine the incidence and transmission of dengue, the authors performed a prospective community-based cohort study in 5,545 children aged 2–14 years in Managua, Nicaragua, between 2004 and 2010. Children were provided with medical care through study physicians who systematically recorded medical consult data, and yearly blood samples were collected to evaluate DENV infection incidence. The incidence of dengue cases observed was 16.1 cases (range 3.4–43.5) per 1,000 person-years (95% CI: 14.5, 17.8), and a pattern of high dengue case incidence every other year was observed. The incidence of DENV infections was 90.2 infections (range 45.2–105.3) per 1,000 person-years (95% CI: 86.1, 94.5). The majority of DENV infections in young children (<6 years old) were primary (60%) and the majority of infections in older children (≥9 years of age) were secondary (82%), as expected. The incidence rate of second DENV infections (121.3 per 1,000 person-years; 95% CI: 102.7, 143.4) was significantly higher than the incidence rate of primary DENV infections (78.8 per 1,000 person-years; 95% CI: 73.2, 84.9). The rigorous analytic methodology used in this study, including incidence reporting in person-years, allows comparison across studies and across different infectious diseases. This study provides important information for understanding dengue epidemiology and informing dengue vaccine policy. PMID:24086788

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. Copyright © 2014 Elsevier B.V. All rights reserved.

Investigational drugs in early development for treating dengue infection.

PubMed

Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam

2016-09-01

Dengue has emerged as the most significant arboviral disease of the current century. A drug for dengue is an urgent unmet need. As conventional drug discovery efforts have not produced any promising clinical candidates, there is a shift toward re-positioning pre-existing drugs for dengue to fast-track dengue drug development. This article provides an update on the current status of recently completed and ongoing dengue drug trials. All dengue drug trials described in this article were identified from a list of >230 trials that were returned upon searching the World Health Organization's International Clinical Trials Registry Platform web portal using the search term 'dengue' on December 31(st), 2015. None of the handful of drugs tested so far has yielded encouraging results. Early trial experience has served to emphasize the challenge of drug testing in the short therapeutic time window available, the need for tools to predict 'high-risk' patients early on and the limitations of the existing pre-clinical model systems. Significant investment of efforts and resources is a must before the availability of a safe, effective and inexpensive dengue drug becomes a reality. Currently, supportive fluid therapy remains the only option available for dengue treatment.

Indices of anti-dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase.

PubMed

Posadas-Mondragón, Araceli; Aguilar-Faisal, José Leopoldo; Chávez-Negrete, Adolfo; Guillén-Salomón, Edith; Alcántara-Farfán, Verónica; Luna-Rojas, Lucero; Ávila-Trejo, Amanda Marineth; Del Carmen Pacheco-Yépez, Judith

2017-10-01

Heterologous secondary infections are at increased risk of developing dengue hemorrhagic fever (DHF) because of antibody-dependent enhancement (ADE). IgG subclasses can fix and activate complement and bind to Fcɣ receptors. These factors may also play an important role in the development of ADE and thus in the pathogenesis of DHF. The aim of this study was to analyze the indices of anti-dengue IgG subclasses in adult patients with febrile and hemorrhagic dengue in the acute phase. In 2013, 129 patients with dengue fever (DF) and 57 with DHF in Veracruz, Mexico were recruited for this study and anti-dengue IgM and IgG determined by capture ELISA. Anti-dengue IgG subclasses were detected by indirect ELISA. Anti-dengue IgG2 and IgG3 subclasses were detected in patients with dengue. IgG1 increased significantly in the sera of patients with both primary and secondary infections and DHF, but was higher in patients with secondary infections. The IgG4 subclass index was significantly higher in the sera of patients with DHF than in that of those with DF, who were in the early and late acute phase of both primary and secondary infection. In conclusion, indices of subclasses IgG1 and IgG4 were higher in patients with DHF. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Discovery of fifth serotype of dengue virus (DENV-5): A new public health dilemma in dengue control.

PubMed

Mustafa, M S; Rasotgi, V; Jain, S; Gupta, V

2015-01-01

Dengue fever is a re-emerging public health problem with two-fifths of the world population being at risk of infection. Till now, dengue fever was believed to be caused by four different serotypes. The fifth variant DENV-5 has been isolated in October 2013. This serotype follows the sylvatic cycle unlike the other four serotypes which follow the human cycle. The likely cause of emergence of the new serotype could be genetic recombination, natural selection and genetic bottlenecks. There is no indication of the presence of DENV-5 in India. Recent clinical trials with the promising Chimerivax tetravalent vaccine suffered a setback. Discovery of DENV-5 and more such sylvatic strains in future may further impede the Dengue Vaccine Initiative. Integrated Vector Management holds the key to sustainable dengue control. Further epidemiological and ecological studies are needed to detect additional sylvatic dengue strains.

Climate influence on dengue epidemics in Puerto Rico.

PubMed

Jury, Mark R

2008-10-01

The variability of the insect-borne disease dengue in Puerto Rico was studied in relation to climatic variables in the period 1979-2005. Annual and monthly reported dengue cases were compared with precipitation and temperature data. Results show that the incidence of dengue in Puerto Rico was relatively constant over time despite global warming, possibly due to the offsetting effects of declining rainfall, improving health care and little change in population. Seasonal fluctuations of dengue were driven by rainfall increases from May to November. Year-to-year variability in dengue cases was positively related to temperature, but only weakly associated with local rainfall and an index of El Nino Southern Oscillation (ENSO). Climatic conditions were mapped with respect to dengue cases and patterns in high and low years were compared. During epidemics, a low pressure system east of Florida draws warm humid air over the northwestern Caribbean. Long-term trends in past observed and future projected rainfall and temperatures were studied. Rainfall has declined slowly, but temperatures in the Caribbean are rising with the influence of global warming. Thus, dengue may increase in the future, and it will be necessary to anticipate dengue epidemics using climate forecasts, to reduce adverse health impacts.

Dengue Knowledge and Preventive Practices in Iquitos, Peru

PubMed Central

Paz-Soldán, Valerie A.; Morrison, Amy C.; Cordova Lopez, Jhonny J.; Lenhart, Audrey; Scott, Thomas W.; Elder, John P.; Sihuincha, Moises; Kochel, Tadeusz J.; Halsey, Eric S.; Astete, Helvio; McCall, Philip J.

2015-01-01

As part of a cluster-randomized trial to evaluate insecticide-treated curtains for dengue prevention in Iquitos, Peru, we surveyed 1,333 study participants to examine knowledge and reported practices associated with dengue and its prevention. Entomological data from 1,133 of these households were linked to the survey. Most participants knew that dengue was transmitted by mosquito bite (85.6%), but only few (18.6%) knew that dengue vectors bite during daytime. Most commonly recognized dengue symptoms were fever (86.6%), headache (76.4%), and muscle/joint pain (67.9%). Most commonly reported correct practices for mosquito control were cleaning homes (61.6%), using insecticide sprays (23%), and avoiding having standing water at home (12.3%). Higher education was associated with higher knowledge about dengue, including transmission and vector control. Higher socioeconomic status was associated with increased reported use of preventive practices requiring money expenditure. We were less likely to find Aedes aegypti eggs, larvae, or pupae in households that had < 5-year-old children at home. Although dengue has been transmitted in Iquitos since the 1990s and the Regional Health Authority routinely fumigates households, treats domestic water containers with larvicide, and issues health education messages through mass media, knowledge of dengue transmission and household practices for prevention could be improved. PMID:26503276

Dengue expansion in Africa-not recognized or not happening?

PubMed

Jaenisch, Thomas; Junghanss, Thomas; Wills, Bridget; Brady, Oliver J; Eckerle, Isabella; Farlow, Andrew; Hay, Simon I; McCall, Philip J; Messina, Jane P; Ofula, Victor; Sall, Amadou A; Sakuntabhai, Anavaj; Velayudhan, Raman; Wint, G R William; Zeller, Herve; Margolis, Harold S; Sankoh, Osman

2014-10-01

An expert conference on Dengue in Africa was held in Accra, Ghana, in February 2013 to consider key questions regarding the possible expansion of dengue in Africa. Four key action points were highlighted to advance our understanding of the epidemiology of dengue in Africa. First, dengue diagnostic tools must be made more widely available in the healthcare setting in Africa. Second, representative data need to be collected across Africa to uncover the true burden of dengue. Third, established networks should collaborate to produce these types of data. Fourth, policy needs to be informed so the necessary steps can be taken to provide dengue vector control and health services.

Dengue Expansion in Africa—Not Recognized or Not Happening?

PubMed Central

Junghanss, Thomas; Wills, Bridget; Brady, Oliver J.; Eckerle, Isabella; Farlow, Andrew; Hay, Simon I.; McCall, Philip J.; Messina, Jane P.; Ofula, Victor; Sall, Amadou A.; Sakuntabhai, Anavaj; Velayudhan, Raman; Wint, G.R. William; Zeller, Herve; Margolis, Harold S.; Sankoh, Osman

2014-01-01

An expert conference on Dengue in Africa was held in Accra, Ghana, in February 2013 to consider key questions regarding the possible expansion of dengue in Africa. Four key action points were highlighted to advance our understanding of the epidemiology of dengue in Africa. First, dengue diagnostic tools must be made more widely available in the healthcare setting in Africa. Second, representative data need to be collected across Africa to uncover the true burden of dengue. Third, established networks should collaborate to produce these types of data. Fourth, policy needs to be informed so the necessary steps can be taken to provide dengue vector control and health services. PMID:25271370

Deep vein thrombosis associated with dengue fever.

PubMed

Roy, Amrita; Chaudhuri, Jasodhara; Chakraborty, Swapna

2013-11-08

Hemorrhagic manifestations are common with Dengue but thrombotic events are uncommonly reported. 11-year-old boy who presented with ileo-femoral deep vein thrombosis associated with serologically confirmed infection with DEN1 dengue virus. There was no other history or investigation suggestive of a procoagulant state. Successfully treated with enoxaparin and warfarin. Thrombotic complications are possible with dengue infection.

Neurological Complications in a Polynesian Traveler with Dengue.

PubMed

Doi, Maegan Lm; Tatsuno, Sydney Y; Singh, Gurdev; Tatsuno, Eric M; Mau, Marjorie M

2017-10-01

In recent times, there has been an increased focus on mosquito-borne Flaviviruses, in particular dengue and Zika. With the reappearance of dengue in Hawai'i and the mainland United States (US), clinicians should be aware of both the common presentations of dengue, as well as other less common complications associated with the disease. Dengue can result in neurologic disorders such as encephalopathy, encephalitis, immune-mediated syndromes, neuromuscular dysfunction, and neuro-ophthalmologic disorders. We present an interesting case of dengue that initially presented with classic symptoms (arthropathy, biphasic fever, and rash) and subsequently developed into a neurologic movement disorder with muscle tightening and twitching of the face, chest, and extremities. We review and update the epidemiology, biology, the clinical presentations including the neurologic complications associated with dengue, as well as their management and areas of future study in this field.

Advances in using Internet searches to track dengue

PubMed Central

Yang, Shihao; Kou, Samuel C.; Brownstein, John S.; Brooke, Nicholas

2017-01-01

Dengue is a mosquito-borne disease that threatens over half of the world’s population. Despite being endemic to more than 100 countries, government-led efforts and tools for timely identification and tracking of new infections are still lacking in many affected areas. Multiple methodologies that leverage the use of Internet-based data sources have been proposed as a way to complement dengue surveillance efforts. Among these, dengue-related Google search trends have been shown to correlate with dengue activity. We extend a methodological framework, initially proposed and validated for flu surveillance, to produce near real-time estimates of dengue cases in five countries/states: Mexico, Brazil, Thailand, Singapore and Taiwan. Our result shows that our modeling framework can be used to improve the tracking of dengue activity in multiple locations around the world. PMID:28727821

Clinical profile and warning sign finding in children with severe dengue and non-severe dengue

NASA Astrophysics Data System (ADS)

Adam, A. S.; Pasaribu, S.; Wijaya, H.; Pasaribu, A. P.

2018-03-01

Dengue fever is one of the most important emerging vector-borne viral diseases. Approximately 500,000 out of 100 million cases develop to severe dengue infection. Patient with severe dengue (SD) can be predicted by clinical profile, laboratory and warning sign which could be saved by early interventions.This was a retrospective descriptive-analytic study to investigate clinical manifestations, laboratory and warning signs ofchildren with dengue infection in Haji Adam Malik hospital during January 2014–May 2016. Through medical records, we had selected 140 cases which fulfilled research criteria.Cases were classified as SD (n=28) and NSD (n=112). Most common clinical manifestations for NSD were abdominal pain (39.3%), myalgia (39.3%), headache (37.1%), mucosal bleeding (36.4%) while for SD were shock (15.7%), mucosal bleeding (15.7%), clinical fluid accumulation (15%), shortness of breath (14.3%). SGPT >1000IU/L (5 cases), SGOT >1000IU/L (9 cases), PT (10 cases) and aPTT (16 cases) were abnormal in SD. Severe dengue was frequently found in the range of white cell count 1000-4000/L and platelet count 20,000-50,000mm/uL. Clinical manifestations, warning sign, and laboratoryfinding, were different between SD and NSD.

Current Status of Dengue Therapeutics Research and Development.

PubMed

Low, Jenny G H; Ooi, Eng Eong; Vasudevan, Subhash G

2017-03-01

Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Vitamin D serostatus and dengue fever progression to dengue hemorrhagic fever/dengue shock syndrome.

PubMed

Villamor, E; Villar, L A; Lozano, A; Herrera, V M; Herrán, O F

2017-10-01

Vitamin D could modulate pathways leading to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). We examined the associations of serum total 25-hydroxy vitamin D [25(OH)D] and vitamin D binding protein (VDBP) concentrations in patients with uncomplicated dengue fever (DF) with risk of progression to DHF/DSS. In a case-control study nested in a cohort of DF patients who were followed during the acute episode in Bucaramanga, Colombia, we compared 25(OH)D and VDBP at onset of fever between 110 cases who progressed to DHF/DSS and 235 DF controls who did not progress. 25(OH)D concentrations were also compared between the acute sample and a sample collected >1 year post-convalescence in a subgroup. Compared with 25(OH)D ⩾75 nmol/l, adjusted odds ratios (95% CI) for progression were 0·44 (0·22-0·88) and 0·13 (0·02-1·05) for 50 to 75 nmol/l (vitamin D insufficiency) and <50 nmol/l (vitamin D deficiency), respectively (P, trend = 0·003). Mean 25(OH)D concentrations were much lower post-convalescence compared with the acute episode, regardless of case status. Compared with controls, mean VDBP was non-significantly lower in cases. We conclude that low serum 25(OH)D concentrations in DF patients predict decreased odds of progression to DHF/DSS.

Internal travel and risk of dengue transmission in Colombia.

PubMed

Chaparro, Pablo E; de la Hoz, Fernando; Lozano Becerra, Juan C; Repetto, Silvia A; Alba Soto, Catalina D

2014-09-01

Human behavior plays a key role in the dynamics of dengue transmission. However, research on the relationship between human movement and dengue transmission within endemic countries is limited. From January 2008 to December 2011, the authors of this study conducted a retrospective analysis of imported dengue infections in Bogotá, Colombia. Bogotá is a vector-transmission-free city that is also the capital district and most populated municipality in Colombia. The study revealed that 1) Bogotá inhabitants acquired dengue infection in diverse localities throughout the country but the largest proportion of cases (35.6%) were contracted at popular tourist destinations in dengue-endemic areas near Bogotá (<200-km radius from city limits), and 2) the number of imported dengue cases increased after major holidays, a transmission pattern not seen in dengue-endemic areas, where disease incidence correlates with rainy periods. It is therefore recommended that physicians consider the effect of travel when diagnosing their patients' illnesses, especially outside dengue-endemic areas where diagnosis of the disease can be challenging due to its nonspecific symptoms. The study also showed that analysis of dengue cases imported to regions free of vector transmission can generate an evidence-based model for characterizing the impact of human movement on the spread of diseases like dengue in countries where they are endemic.

Spatial Analysis of Dengue Seroprevalence and Modeling of Transmission Risk Factors in a Dengue Hyperendemic City of Venezuela.

PubMed

Vincenti-Gonzalez, Maria F; Grillet, María-Eugenia; Velasco-Salas, Zoraida I; Lizarazo, Erley F; Amarista, Manuel A; Sierra, Gloria M; Comach, Guillermo; Tami, Adriana

2017-01-01

Dengue virus (DENV) transmission is spatially heterogeneous. Hence, to stratify dengue prevalence in space may be an efficacious strategy to target surveillance and control efforts in a cost-effective manner particularly in Venezuela where dengue is hyperendemic and public health resources are scarce. Here, we determine hot spots of dengue seroprevalence and the risk factors associated with these clusters using local spatial statistics and a regression modeling approach. From August 2010 to January 2011, a community-based cross-sectional study of 2012 individuals in 840 households was performed in high incidence neighborhoods of a dengue hyperendemic city in Venezuela. Local spatial statistics conducted at household- and block-level identified clusters of recent dengue seroprevalence (39 hot spot households and 9 hot spot blocks) in all neighborhoods. However, no clusters were found for past dengue seroprevalence. Clustering of infection was detected at a very small scale (20-110m) suggesting a high disease focal aggregation. Factors associated with living in a hot spot household were occupation (being a domestic worker/housewife (P = 0.002), lower socio-economic status (living in a shack (P<0.001), sharing a household with <7 people (P = 0.004), promoting potential vector breeding sites (storing water in containers (P = 0.024), having litter outdoors (P = 0.002) and mosquito preventive measures (such as using repellent, P = 0.011). Similarly, low socio-economic status (living in crowded conditions, P<0.001), having an occupation of domestic worker/housewife (P = 0.012) and not using certain preventive measures against mosquitoes (P<0.05) were directly associated with living in a hot spot block. Our findings contribute to a better comprehension of the spatial dynamics of dengue by assessing the relationship between disease clusters and their risk factors. These results can inform health authorities in the design of surveillance and control activities. Focalizing

Spatial Analysis of Dengue Seroprevalence and Modeling of Transmission Risk Factors in a Dengue Hyperendemic City of Venezuela

PubMed Central

Vincenti-Gonzalez, Maria F.; Grillet, María-Eugenia; Velasco-Salas, Zoraida I.; Lizarazo, Erley F.; Amarista, Manuel A.; Sierra, Gloria M.; Comach, Guillermo

2017-01-01

Background Dengue virus (DENV) transmission is spatially heterogeneous. Hence, to stratify dengue prevalence in space may be an efficacious strategy to target surveillance and control efforts in a cost-effective manner particularly in Venezuela where dengue is hyperendemic and public health resources are scarce. Here, we determine hot spots of dengue seroprevalence and the risk factors associated with these clusters using local spatial statistics and a regression modeling approach. Methodology/Principal Findings From August 2010 to January 2011, a community-based cross-sectional study of 2012 individuals in 840 households was performed in high incidence neighborhoods of a dengue hyperendemic city in Venezuela. Local spatial statistics conducted at household- and block-level identified clusters of recent dengue seroprevalence (39 hot spot households and 9 hot spot blocks) in all neighborhoods. However, no clusters were found for past dengue seroprevalence. Clustering of infection was detected at a very small scale (20-110m) suggesting a high disease focal aggregation. Factors associated with living in a hot spot household were occupation (being a domestic worker/housewife (P = 0.002), lower socio-economic status (living in a shack (P<0.001), sharing a household with <7 people (P = 0.004), promoting potential vector breeding sites (storing water in containers (P = 0.024), having litter outdoors (P = 0.002) and mosquito preventive measures (such as using repellent, P = 0.011). Similarly, low socio-economic status (living in crowded conditions, P<0.001), having an occupation of domestic worker/housewife (P = 0.012) and not using certain preventive measures against mosquitoes (P<0.05) were directly associated with living in a hot spot block. Conclusions/Significance Our findings contribute to a better comprehension of the spatial dynamics of dengue by assessing the relationship between disease clusters and their risk factors. These results can inform health authorities

Seroprevalence of acute dengue in a Malaysian tertiary medical centre

PubMed Central

Ding, Chuan Hun; Rashid, Zetti Zainol; Rahman, Md. Mostafizur; Khang, NanFeng; Low, Wan Ngor; Hussin, Nurabrar; Marzuki, Melissa Iqlima; Jaafar, Alyaa Nadhira; Roslan, Nurul Ain’ Nabilla; Chandrasekaran, Terukumar

2016-01-01

Objectives: The aims of this study were to determine the seroprevalence of acute dengue in Universiti Kebangsaan Malaysia (UKM) Medical Centre and its correlation with selected haematological and biochemical parameters. Methods: This cross-sectional study was conducted from January to June 2015. A patient was serologically diagnosed with acute dengue if the dengue virus IgG, IgM or NS-1 antigen was reactive. Results: Out of 1,774 patients suspected to have acute dengue, 1,153 were serologically diagnosed with the infection, resulting in a seroprevalence of 64.9%. Dengue-positive patients had a lower mean platelet count (89 × 109/L) compared to the dengue-negative patients (171 × 109/L) (p<0.0001). The mean total white cell count was also lower in the dengue-positive cases (4.7 × 109/L vs. 7.2 × 109/L; p<0.0001). The mean haematocrit was higher in patients with acute dengue (42.5% vs. 40.0%; p<0.0001). Likewise, the serum alanine transaminase level was also higher in patients with acute dengue (108 U/L vs. 54 U/L; p<0.0001). Conclusions: Dengue is very prevalent in UKM Medical Centre as most patients suspected to have acute dengue had serological evidence of the infection. The platelet count was the single most likely parameter to be abnormal (i.e. low) in patients with acute dengue. PMID:27182269

Clinical Score to Differentiate Scrub Typhus and Dengue: A Tool to Differentiate Scrub Typhus and Dengue.

PubMed

Mitra, Shubhanker; Gautam, Ira; Jambugulam, Mohan; Abhilash, Kundavaram Paul Prabhakar; Jayaseeelan, Vishalakshi

2017-01-01

Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC) was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%), total white blood cell count (<4000, 4001-7000 and >7000 cells/cumm), hemoglobin (≤14 and >14 g/dL), total bilirubin (<2 and ≥2 mg/dL), serum glutamic oxaloacetic transaminase (>200 and ≥200 IU/dL), and altered sensorium (present or absent). Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval) for model 2 was 0.84 (0.79-0.89). At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. In areas of high burden of ST and dengue, model 2 (the "clinical score to differentiate scrub typhus and dengue fever") is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.

Assessing changes in knowledge, attitude and practices on dengue diagnosis and management among primary care physicians after the largest dengue epidemic in Singapore.

PubMed

Pang, Junxiong; Hildon, Zoe Jane-Lara; Thein, Tun Linn; Jin, Jing; Leo, Yee Sin

2017-06-15

Dengue results in high morbidity and mortality globally. The knowledge, attitude and practices (KAP) of dengue management, including diagnosis, among primary care physicians (PCPs) are important to reduce dengue transmission and burden. However, there is a lack of understanding on the impact of dengue epidemic on dengue management. Hence, the aim of this study is to examine the changes in KAP on dengue management among PCPs before and after the largest dengue epidemic in 2013 in Singapore. Surveys were mailed to 2000 and 1514 PCPs registered under the Singapore Medical Council in March of year 2011 and 2014, respectively. Survey data were then collected between April and June of that year. Chi-square or Fisher's exact test was used for comparing categorical variables. A multivariate logistic regression model was implemented to determine independent factors for frequent use of dengue diagnostic tests (DDTs). All tests were conducted at 5% level of significance. Adjusted odds ratio and corresponding 95% confidence intervals were reported, where applicable. Qualitative data were descriptively coded for themes and analysis. Among PCPs surveyed in 2011 and 2014, 89.9% and 86% had good knowledge on dengue management respectively. The usage of DDTs had increased significantly in 2014 (N = 164;56%) as compared to 2011 (N = 107;29.5%) in both private and public clinics (p < 0.001). Dengue Duo point-of-care test (POCT) kits was independently associated with frequent use of DDTs (adjusted odds ratio = 2.15; 95% confidence interval = 1.25-3.69). There was a significant reduction in referral of dengue patients to hospital (31.4% in 2011; 13.3% in 2014; p < 0.001), and a significant increase in frequency of clinic follow-ups (18.4% in 2011; 28.5% in 2014; p = 0.003). One key theme highlighted was that dengue management can be improved with availability of POCT kit, better awareness of the disease and any revised clinical guidelines. The knowledge on dengue

Analysis of Dengue Serotype 4 in Sri Lanka during the 2012-2013 Dengue Epidemic.

PubMed

Uehara, Anna; Tissera, Hasitha Aravinda; Bodinayake, Champica K; Amarasinghe, Ananda; Nagahawatte, Ajith; Tillekeratne, L Gayani; Cui, Jie; Reller, Megan E; Palihawadana, Paba; Gunasena, Sunethra; Desilva, Aruna Dharshan; Wilder-Smith, Annelies; Gubler, Duane J; Woods, Christopher W; Sessions, October M

2017-07-01

The four serotypes of dengue virus (DENV-1, -2, -3, and -4) have had a rapidly expanding geographic range and are now endemic in over 100 tropical and subtropical countries. Sri Lanka has experienced periodic dengue outbreaks since the 1960s, but since 1989 epidemics have become progressively larger and associated with more severe disease. The dominant virus in the 2012 epidemic was DENV-1, but DENV-4 infections were also commonly observed. DENV-4 transmission was first documented in Sri Lanka when it was isolated from a traveler in 1978, but has been comparatively uncommon since dengue surveillance began in the early 1980s. To better understand the molecular epidemiology of DENV-4 infections in Sri Lanka, we conducted whole-genome sequencing on dengue patient samples from two different geographic locations. Phylogenetic analysis indicates that all sequenced DENV-4 strains belong to genotype 1 and are most closely related to DENV-4 viruses previously found in Sri Lanka and those recently found to be circulating in India and Pakistan.

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

Re-assess Vector Indices Threshold as an Early Warning Tool for Predicting Dengue Epidemic in a Dengue Non-endemic Country

PubMed Central

Hsu, Pi-Shan; Chen, Chaur-Dong; Lian, Ie-Bin; Chao, Day-Yu

2015-01-01

Background Despite dengue dynamics being driven by complex interactions between human hosts, mosquito vectors and viruses that are influenced by climate factors, an operational model that will enable health authorities to anticipate the outbreak risk in a dengue non-endemic area has not been developed. The objectives of this study were to evaluate the temporal relationship between meteorological variables, entomological surveillance indices and confirmed dengue cases; and to establish the threshold for entomological surveillance indices including three mosquito larval indices [Breteau (BI), Container (CI) and House indices (HI)] and one adult index (AI) as an early warning tool for dengue epidemic. Methodology/Principal Findings Epidemiological, entomological and meteorological data were analyzed from 2005 to 2012 in Kaohsiung City, Taiwan. The successive waves of dengue outbreaks with different magnitudes were recorded in Kaohsiung City, and involved a dominant serotype during each epidemic. The annual indigenous dengue cases usually started from May to June and reached a peak in October to November. Vector data from 2005–2012 showed that the peak of the adult mosquito population was followed by a peak in the corresponding dengue activity with a lag period of 1–2 months. Therefore, we focused the analysis on the data from May to December and the high risk district, where the inspection of the immature and mature mosquitoes was carried out on a weekly basis and about 97.9% dengue cases occurred. The two-stage model was utilized here to estimate the risk and time-lag effect of annual dengue outbreaks in Taiwan. First, Poisson regression was used to select the optimal subset of variables and time-lags for predicting the number of dengue cases, and the final results of the multivariate analysis were selected based on the smallest AIC value. Next, each vector index models with selected variables were subjected to multiple logistic regression models to examine the

Dengue Contingency Planning: From Research to Policy and Practice

PubMed Central

Runge-Ranzinger, Silvia; Kroeger, Axel; Olliaro, Piero; McCall, Philip J.; Sánchez Tejeda, Gustavo; Lloyd, Linda S.; Hakim, Lokman; Bowman, Leigh R.; Horstick, Olaf; Coelho, Giovanini

2016-01-01

Background Dengue is an increasingly incident disease across many parts of the world. In response, an evidence-based handbook to translate research into policy and practice was developed. This handbook facilitates contingency planning as well as the development and use of early warning and response systems for dengue fever epidemics, by identifying decision-making processes that contribute to the success or failure of dengue surveillance, as well as triggers that initiate effective responses to incipient outbreaks. Methodology/Principal findings Available evidence was evaluated using a step-wise process that included systematic literature reviews, policymaker and stakeholder interviews, a study to assess dengue contingency planning and outbreak management in 10 countries, and a retrospective logistic regression analysis to identify alarm signals for an outbreak warning system using datasets from five dengue endemic countries. Best practices for managing a dengue outbreak are provided for key elements of a dengue contingency plan including timely contingency planning, the importance of a detailed, context-specific dengue contingency plan that clearly distinguishes between routine and outbreak interventions, surveillance systems for outbreak preparedness, outbreak definitions, alert algorithms, managerial capacity, vector control capacity, and clinical management of large caseloads. Additionally, a computer-assisted early warning system, which enables countries to identify and respond to context-specific variables that predict forthcoming dengue outbreaks, has been developed. Conclusions/Significance Most countries do not have comprehensive, detailed contingency plans for dengue outbreaks. Countries tend to rely on intensified vector control as their outbreak response, with minimal focus on integrated management of clinical care, epidemiological, laboratory and vector surveillance, and risk communication. The Technical Handbook for Surveillance, Dengue Outbreak

The Effects of Weather and Climate Change on Dengue

PubMed Central

Colón-González, Felipe J.; Fezzi, Carlo; Lake, Iain R.; Hunter, Paul R.

2013-01-01

Background There is much uncertainty about the future impact of climate change on vector-borne diseases. Such uncertainty reflects the difficulties in modelling the complex interactions between disease, climatic and socioeconomic determinants. We used a comprehensive panel dataset from Mexico covering 23 years of province-specific dengue reports across nine climatic regions to estimate the impact of weather on dengue, accounting for the effects of non-climatic factors. Methods and Findings Using a Generalized Additive Model, we estimated statistically significant effects of weather and access to piped water on dengue. The effects of weather were highly nonlinear. Minimum temperature (Tmin) had almost no effect on dengue incidence below 5°C, but Tmin values above 18°C showed a rapidly increasing effect. Maximum temperature above 20°C also showed an increasing effect on dengue incidence with a peak around 32°C, after which the effect declined. There is also an increasing effect of precipitation as it rose to about 550 mm, beyond which such effect declines. Rising access to piped water was related to increasing dengue incidence. We used our model estimations to project the potential impact of climate change on dengue incidence under three emission scenarios by 2030, 2050, and 2080. An increase of up to 40% in dengue incidence by 2080 was estimated under climate change while holding the other driving factors constant. Conclusions Our results indicate that weather significantly influences dengue incidence in Mexico and that such relationships are highly nonlinear. These findings highlight the importance of using flexible model specifications when analysing weather–health interactions. Climate change may contribute to an increase in dengue incidence. Rising access to piped water may aggravate dengue incidence if it leads to increased domestic water storage. Climate change may therefore influence the success or failure of future efforts against dengue. PMID:24244765

The effects of weather and climate change on dengue.

PubMed

Colón-González, Felipe J; Fezzi, Carlo; Lake, Iain R; Hunter, Paul R

2013-11-01

There is much uncertainty about the future impact of climate change on vector-borne diseases. Such uncertainty reflects the difficulties in modelling the complex interactions between disease, climatic and socioeconomic determinants. We used a comprehensive panel dataset from Mexico covering 23 years of province-specific dengue reports across nine climatic regions to estimate the impact of weather on dengue, accounting for the effects of non-climatic factors. Using a Generalized Additive Model, we estimated statistically significant effects of weather and access to piped water on dengue. The effects of weather were highly nonlinear. Minimum temperature (Tmin) had almost no effect on dengue incidence below 5 °C, but Tmin values above 18 °C showed a rapidly increasing effect. Maximum temperature above 20 °C also showed an increasing effect on dengue incidence with a peak around 32 °C, after which the effect declined. There is also an increasing effect of precipitation as it rose to about 550 mm, beyond which such effect declines. Rising access to piped water was related to increasing dengue incidence. We used our model estimations to project the potential impact of climate change on dengue incidence under three emission scenarios by 2030, 2050, and 2080. An increase of up to 40% in dengue incidence by 2080 was estimated under climate change while holding the other driving factors constant. Our results indicate that weather significantly influences dengue incidence in Mexico and that such relationships are highly nonlinear. These findings highlight the importance of using flexible model specifications when analysing weather-health interactions. Climate change may contribute to an increase in dengue incidence. Rising access to piped water may aggravate dengue incidence if it leads to increased domestic water storage. Climate change may therefore influence the success or failure of future efforts against dengue.

Dengue Contingency Planning: From Research to Policy and Practice.

PubMed

Runge-Ranzinger, Silvia; Kroeger, Axel; Olliaro, Piero; McCall, Philip J; Sánchez Tejeda, Gustavo; Lloyd, Linda S; Hakim, Lokman; Bowman, Leigh R; Horstick, Olaf; Coelho, Giovanini

2016-09-01

Dengue is an increasingly incident disease across many parts of the world. In response, an evidence-based handbook to translate research into policy and practice was developed. This handbook facilitates contingency planning as well as the development and use of early warning and response systems for dengue fever epidemics, by identifying decision-making processes that contribute to the success or failure of dengue surveillance, as well as triggers that initiate effective responses to incipient outbreaks. Available evidence was evaluated using a step-wise process that included systematic literature reviews, policymaker and stakeholder interviews, a study to assess dengue contingency planning and outbreak management in 10 countries, and a retrospective logistic regression analysis to identify alarm signals for an outbreak warning system using datasets from five dengue endemic countries. Best practices for managing a dengue outbreak are provided for key elements of a dengue contingency plan including timely contingency planning, the importance of a detailed, context-specific dengue contingency plan that clearly distinguishes between routine and outbreak interventions, surveillance systems for outbreak preparedness, outbreak definitions, alert algorithms, managerial capacity, vector control capacity, and clinical management of large caseloads. Additionally, a computer-assisted early warning system, which enables countries to identify and respond to context-specific variables that predict forthcoming dengue outbreaks, has been developed. Most countries do not have comprehensive, detailed contingency plans for dengue outbreaks. Countries tend to rely on intensified vector control as their outbreak response, with minimal focus on integrated management of clinical care, epidemiological, laboratory and vector surveillance, and risk communication. The Technical Handbook for Surveillance, Dengue Outbreak Prediction/ Detection and Outbreak Response seeks to provide countries

Clinical Profile of Atypical Manifestations of Dengue Fever.

PubMed

Pothapregada, Sriram; Kamalakannan, Banupriya; Thulasingam, Mahalakshmy

2016-06-01

To study the clinical profile and outcome of the atypical manifestations of dengue fever in children. All children (0-12 y of age) diagnosed and confirmed as dengue fever at a tertiary care hospital at Puducherry, between the 1st of August 2012 and January 31st 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization (WHO) guidelines 2011 for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies and the data was analyzed using SPSS 16.0 statistical software. Out of 254 children admitted with dengue fever, non-severe dengue and severe dengue were seen in 62.6 % and 37.4 % respectively. Atypical manifestations were seen in 106 cases (41.7 %). Mean age of presentation was 6.9(3.3) y. M: F ratio was 1.2:1. The common manifestations of severe dengue infection were shock (37.4 %), bleeding (20.1 %) and multi-organ dysfunction (2.4 %). The most common atypical manifestations of dengue fever were lymphadenopathy (41.7 %), splenomegaly (21.2 %), biphasic fever (18.1 %), hepatitis (11.4 %), febrile diarrhea (6.3 %), refractory shock (2.4 %) and impaired consciousness (1.9 %). The other atypical manifestations present were portal hypertension, acalculous cholecystitis, appendicitis, acute respiratory distress syndrome (ARDS), myocarditis, pericardial effusion, paroxysmal supraventricular tachycardia (PSVT), myositis, acute kidney injury (AKI), hemophagocytic syndrome and disseminated intravascular coagulopathy (DIC). Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.4 %) and out of them four presented with impaired consciousness (66.6 %). The common causes for poor outcome were multiorgan failure, encephalopathy and refractory shock. The atypical manifestations of dengue fever are no more a rare entity. Clinicians should have a high index of suspicion and vigilance for atypical manifestations of

Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Path to a Dengue Vaccine: Learning from Human Natural Dengue Infection Studies and Vaccine Trials.

PubMed

de Silva, Aravinda M; Harris, Eva

2018-06-01

Dengue virus (DENV) is the most common arthropod-borne viral disease of humans. Although effective vaccines exist against other flaviviral diseases like yellow fever and Japanese encephalitis, dengue vaccine development is complicated by the presence of four virus serotypes and the possibility of partial immunity enhancing dengue disease severity. Several live attenuated dengue vaccines are being tested in human clinical trials. Initial results are mixed, with variable efficacy depending on DENV serotype and previous DENV exposure. Here, we highlight recent discoveries about the human antibody response to DENV and propose guidelines for advancing development of safe and effective dengue vaccines. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Dengue Dynamics and Vaccine Cost-Effectiveness Analysis in the Philippines

PubMed Central

Shim, Eunha

2016-01-01

Dengue is one of the most problematic vector-borne diseases in the Philippines, with an estimated 842,867 cases resulting in medical costs of $345 million U.S. dollars annually. In December 2015, the first dengue vaccine, known as chimeric yellow fever virus–dengue virus tetravalent dengue vaccine, was approved for use in the Philippines and is given to children 9 years of age. To estimate the cost-effectiveness of dengue vaccination in the Philippines, we developed an age-structured model of dengue transmission and vaccination. Using our model, we compared two vaccination scenarios entailing routine vaccination programs both with and without catch-up vaccination. Our results indicate that the higher the cost of vaccination, the less cost-effective the dengue vaccination program. With the current dengue vaccination program that vaccinates children 9 years of age, dengue vaccination is cost-effective for vaccination costs up to $70 from a health-care perspective and up to $75 from a societal perspective. Under a favorable scenario consisting of 1 year of catch-up vaccinations that target children 9–15 years of age, followed by regular vaccination of 9-year-old children, vaccination is cost-effective at costs up to $72 from a health-care perspective and up to $78 from a societal perspective. In general, dengue vaccination is expected to reduce the incidence of both dengue fever and dengue hemorrhagic fever /dengue shock syndrome. Our results demonstrate that even at relatively low vaccine efficacies, age-targeted vaccination may still be cost-effective provided the vaccination cost is sufficiently low. PMID:27601519

Investigation of spatiotemporal relationship between dengue fever and drought

NASA Astrophysics Data System (ADS)

Lee, Chieh-Han; Yu, Hwa-Lung

2016-04-01

Dengue Fever is a vector-borne disease that is transmitted between human and mosquitos in tropical and sub-tropical regions. Previous studies have found significant relationship between the epidemic of dengue cases and climate variables, especially temperature and precipitation. Besides, the natural phenomena (e.g., drought) are considered that significantly drop the number of dengue cases by killing vector's breeding environment. However, in Kaohsiung City, Taiwan, there are evidences that the temporal pattern of dengue is correlated to drought events. Kaohsiung City experienced two main dengue outbreaks in 2002 and 2014 that both years were confirmed with serious drought. Especially in 2014, Kaohsiung City was suffered from extremely dengue outbreak in 2014 that reported the highest number of dengue cases in the history. Otherwise, another nearby city, Tainan City, had reported the biggest outbreak in 2015. This study constructs the spatiotemporal model of dengue incidences and index of drought events (Standardized Precipitation Index, SPI) based on the distributed lag nonlinear model (DLNM). Other meteorological measures are also included in the analysis.

Prevention and Control Strategies to Counter Dengue Virus Infection.

PubMed

Rather, Irfan A; Parray, Hilal A; Lone, Jameel B; Paek, Woon K; Lim, Jeongheui; Bajpai, Vivek K; Park, Yong-Ha

2017-01-01

Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV) has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus.

Prevention and Control Strategies to Counter Dengue Virus Infection

PubMed Central

Rather, Irfan A.; Parray, Hilal A.; Lone, Jameel B.; Paek, Woon K.; Lim, Jeongheui; Bajpai, Vivek K.; Park, Yong-Ha

2017-01-01

Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV) has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus. PMID:28791258

Attack rates of dengue fever in Swedish travellers.

PubMed

Rocklöv, Joacim; Lohr, Wolfgang; Hjertqvist, Marika; Wilder-Smith, Annelies

2014-06-01

Dengue is endemic in many countries visited by Swedish travellers. We aimed to determine the attack rate of dengue in Swedish travellers and analyse the trends over time and the geographical variation. We obtained the following data from the Swedish Institute for Communicable Disease Control for the y 1995-2010: number of Swedish residents with confirmed dengue, the country and year of infection. We also obtained registers on the Swedish annual air traveller arrivals to dengue endemic areas from the United Nations World Tourist Organization for the time period. We estimated attack rates with 95% confidence intervals (CI). In total, 925 Swedish travellers with confirmed dengue were reported. We found an increasing trend over time for most destinations. The majority of the dengue cases were acquired in Thailand (492 out of 925 travellers; 53%), with an attack rate of 13.6 (95% CI 12.7, 14.4) per 100,000 travellers. However, the 2 highest attack rates per 100,000 travellers were found for Sri Lanka (45.3, 95% CI 34.3, 56.4) and Bangladesh (42.6, 95% CI 23.8, 61.5). Information on attack rates in travellers is more helpful in guiding travel medicine practitioners than reports of absolute numbers, as the latter reflect travel preferences rather than the true risk. Although the majority of dengue infections in Swedish travellers were acquired in Thailand, the attack rates for dengue in travellers to Sri Lanka and Bangladesh were much higher. These data aid in refining information on the risk of dengue in travellers.

Is dengue a threat to the blood supply?

PubMed Central

Teo, D; Ng, L C; Lam, S

2009-01-01

Dengue is the most common arthropod-borne infection worldwide, affecting at least 50 million people every year and endemic in more than 100 countries. The dengue virus is a single-stranded RNA virus with four major serotypes. Infection with one serotype confers homotypic immunity but not heterologous immunity, and secondary infection with another serotype may lead to more severe disease. The major route of transmission occurs through the Aedes aegypti mosquito vector, but dengue has also been transmitted through blood transfusion and organ transplantation. Infection results in a spectrum of clinical illness ranging from asymptomatic infection, undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF) to dengue shock syndrome (DSS). Dengue is spreading rapidly to new areas and with increasing frequency of major outbreaks. A trend has also been observed towards increasing age among infected patients. This will impact blood supply availability as more blood donors are deferred because of dengue infection or exposure to infection. The risk of transmission through transfusion of blood from asymptomatic viraemic donors will also increase. Although screening tests for dengue and effective pathogen reduction processes are now available for the blood supply, the value of implementing these costly measures needs to be carefully considered. Demand for platelets and fresh frozen plasma will rise with increasing number of DHF/DSS. Evidence-based guidelines for the clinical use of these blood components in the management of patients with DHF/DSS have not been well established, and inappropriate use will contribute to the challenges faced by blood services. PMID:19392949

Broad neutralization of wild-type dengue virus isolates following immunization in monkeys with a tetravalent dengue vaccine based on chimeric yellow fever 17D/dengue viruses.

PubMed

Barban, Veronique; Munoz-Jordan, Jorge L; Santiago, Gilberto A; Mantel, Nathalie; Girerd, Yves; Gulia, Sandrine; Claude, Jean-Baptiste; Lang, Jean

2012-08-01

The objective of the study was to evaluate if the antibodies elicited after immunization with a tetravalent dengue vaccine, based on chimeric yellow fever 17D/dengue viruses, can neutralize a large range of dengue viruses (DENV). A panel of 82 DENVs was developed from viruses collected primarily during the last decade in 30 countries and included the four serotypes and the majority of existing genotypes. Viruses were isolated and minimally amplified before evaluation against a tetravalent polyclonal serum generated during vaccine preclinical evaluation in monkey, a model in which protection efficacy of this vaccine has been previously demonstrated (Guirakhoo et al., 2004). Neutralization was observed across all the DENV serotypes, genotypes, geographical origins and isolation years. These data indicate that antibodies elicited after immunization with this dengue vaccine candidate should widely protect against infection with contemporary DENV lineages circulating in endemic countries. Copyright © 2012 Elsevier Inc. All rights reserved.

Household costs of dengue illness: secondary outcomes from a randomised controlled trial of dengue prevention in Guerrero state, Mexico.

PubMed

Legorreta-Soberanis, José; Paredes-Solís, Sergio; Morales-Pérez, Arcadio; Nava-Aguilera, Elizabeth; Serrano-de Los Santos, Felipe René; Dimas-Garcia, Diana Lisseth; Ledogar, Robert J; Cockcroft, Anne; Andersson, Neil

2017-05-30

Dengue is a serious public health problem with an important economic impact. This study used data from a cluster randomised controlled trial of community mobilisation for dengue prevention to estimate the household costs of treatment of dengue illness. It examined the economic impact of the trial intervention in the three coastal regions of Mexico's Guerrero State. The 2010 baseline survey covered households in a random sample of 90 clusters in the coastal regions; the clusters were randomly allocated to intervention or control and re-surveyed in 2012. The surveys asked about dengue cases in the last 12 months, expenditures on their treatment, and work or school days lost by patients and care givers. We did not assign monetary value to days lost, since a lost day to a person of low earning power is of equal or higher value to that person than to one who earns more. The 12,312 households in 2010 reported 1020 dengue cases in the last 12 months (1.9% of the sample population). Most (78%) were ambulatory cases, with a mean cost of USD 51 and 10.8 work/school days, rising to USD 96 and 11.4 work/school days if treated by a private physician. Hospitalised cases cost USD 28-94 in government institutions and USD 392 in private hospitals (excluding additional inpatient charges), as well as 9.6-17.3 work/school days. Dengue cases cost households an estimated 412,825 work/school days throughout the three coastal regions. In the follow up survey, 6.1% (326/5349) of households in intervention clusters and 7.9% (405/5139) in control clusters reported at least one dengue case. The mean of days lost per case was similar in intervention and control clusters, but the number of days lost from dengue and all elements of costs for dengue cases per 1000 population were lower in intervention clusters. If the total population of the three coastal regions had received the intervention, some 149,401 work or school days lost per year could have been prevented. The economic effect of

Management of dengue in Australian travellers: a retrospective multicentre analysis.

PubMed

Tai, Alex Yc; McGuinness, Sarah L; Robosa, Roselle; Turner, David; Huang, G Khai Lin; Leder, Karin; Korman, Tony M; Thevarajan, Irani; Stewardson, Andrew J; Padiglione, Alexander A; Johnson, Douglas F

2017-04-17

To describe the epidemiology, clinical and laboratory features and outcomes of dengue in returned Australian travellers, applying the revised WHO dengue classification (2009) to this population. Retrospective case series analysis of confirmed dengue cases hospitalised at one of four Australian tertiary hospitals, January 2012 - May 2015. Clinical features, laboratory findings and outcomes of patients with dengue; dengue classification according to 2009 WHO guidelines. 208 hospitalised patients (median age, 32 years; range, 4-76 years) were included in the study. Dengue was most frequently acquired in Indonesia (94 patients, 45%) and Thailand (40, 19%). The most common clinical features were fever (98% of patients) and headache (76%). 84 patients (40%) met the WHO criteria for dengue with warning signs, and one the criteria for severe dengue; the most common warning signs were mucosal bleeding (44 patients, 21%) and abdominal pain (43, 21%). Leukopenia (176 patients, 85%), thrombocytopenia (133, 64%), and elevated liver enzyme levels (154, 76%) were the most common laboratory findings. 46 patients (22%) had serological evidence of previous exposure to dengue virus. WHO guidelines were documented as a management benchmark in ten cases (5%); 46 patients (22%) received non-steroidal anti-inflammatory drugs (NSAIDs). A significant proportion of returning Australian travellers hospitalised for dengue have unrecognised warning signs of severe disease. Many received NSAIDs, which can increase the risk of haemorrhage in dengue. As travel to Asia from Australia continues to increase, it is vital for averting serious outcomes that clinicians can recognise and manage dengue.

Dengue Knowledge and Preventive Practices in Iquitos, Peru.

PubMed

Paz-Soldán, Valerie A; Morrison, Amy C; Cordova Lopez, Jhonny J; Lenhart, Audrey; Scott, Thomas W; Elder, John P; Sihuincha, Moises; Kochel, Tadeusz J; Halsey, Eric S; Astete, Helvio; McCall, Philip J

2015-12-01

As part of a cluster-randomized trial to evaluate insecticide-treated curtains for dengue prevention in Iquitos, Peru, we surveyed 1,333 study participants to examine knowledge and reported practices associated with dengue and its prevention. Entomological data from 1,133 of these households were linked to the survey. Most participants knew that dengue was transmitted by mosquito bite (85.6%), but only few (18.6%) knew that dengue vectors bite during daytime. Most commonly recognized dengue symptoms were fever (86.6%), headache (76.4%), and muscle/joint pain (67.9%). Most commonly reported correct practices for mosquito control were cleaning homes (61.6%), using insecticide sprays (23%), and avoiding having standing water at home (12.3%). Higher education was associated with higher knowledge about dengue, including transmission and vector control. Higher socioeconomic status was associated with increased reported use of preventive practices requiring money expenditure. We were less likely to find Aedes aegypti eggs, larvae, or pupae in households that had < 5-year-old children at home. Although dengue has been transmitted in Iquitos since the 1990s and the Regional Health Authority routinely fumigates households, treats domestic water containers with larvicide, and issues health education messages through mass media, knowledge of dengue transmission and household practices for prevention could be improved. © The American Society of Tropical Medicine and Hygiene.

Nine year trends of dengue virus infection in Mumbai, Western India.

PubMed

Shastri, Jayanthi; Williamson, Manita; Vaidya, Nilima; Agrawal, Sachee; Shrivastav, Om

2017-01-01

Dengue virus (DENV) causes a wide range of diseases in humans, from acute febrile illness Dengue fever (DF) to life-threatening Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Factors believed to be responsible for spread of Dengue virus infection include explosive population growth, unplanned urban overpopulation with inadequate public health systems, poor standing water and vector control, climate changes and increased international recreational, business, military travel to endemic areas. All of these factors must be addressed to control the spread of Dengue and other mosquito-borne infections. The detection of Dengue virus RNA by reverse transcriptase PCR (RT-PCR) in human serum or plasma samples is highly indicative of acute Dengue fever. Moreover, the method is able to identify the Dengue virus serotype by demonstrating defined sequence homologies in the viral genomic RNA. During the nine year period of this study analysis, 6767 strongly suspected cases were tested by RT-PCR. 1685 (24.9%) were Dengue PCR positive and confirmed as Dengue cases. Observations on the seasonality were based on the nine year's data as the intensity of sampling was at its maximum during monsoon season. Dengue typing was done on 100 positive samples after storage of Dengue RNA at - 80°C. Dengue serotypes were detected in 69 samples of which Dengue 2 was most predominant. 576 samples were processed for NS1 antigen and PCR simultaneously. 19/576 were positive (3.3 %) for NS1 as well as by PCR. 23/576 samples were negative for NS1 antigen, but were positive by RT-PCR. The remaining 534 samples which were negative for NS1 antigen were also negative by Dengue RT-PCR. In this study we sought to standardize rapid, sensitive, and specific fluorogenic probe-based RT-PCR assay to screen and serotype a representative range of Dengue viruses that are found in and around Mumbai. Qualitative Dengue virus TaqMan assays could have tremendous utility for the epidemiological

Cost of dengue outbreaks: literature review and country case studies.

PubMed

Stahl, Hans-Christian; Butenschoen, Vicki Marie; Tran, Hien Tinh; Gozzer, Ernesto; Skewes, Ronald; Mahendradhata, Yodi; Runge-Ranzinger, Silvia; Kroeger, Axel; Farlow, Andrew

2013-11-06

Dengue disease surveillance and vector surveillance are presumed to detect dengue outbreaks at an early stage and to save--through early response activities--resources, and reduce the social and economic impact of outbreaks on individuals, health systems and economies. The aim of this study is to unveil evidence on the cost of dengue outbreaks. Economic evidence on dengue outbreaks was gathered by conducting a literature review and collecting information on the costs of recent dengue outbreaks in 4 countries: Peru, Dominican Republic, Vietnam, and Indonesia. The literature review distinguished between costs of dengue illness including cost of dengue outbreaks, cost of interventions and cost-effectiveness of interventions. Seventeen publications on cost of dengue showed a large range of costs from 0.2 Million US$ in Venezuela to 135.2 Million US$ in Brazil. However, these figures were not standardized to make them comparable. Furthermore, dengue outbreak costs are calculated differently across the publications, and cost of dengue illness is used interchangeably with cost of dengue outbreaks. Only one paper from Australia analysed the resources saved through active dengue surveillance. Costs of vector control interventions have been reported in 4 studies, indicating that the costs of such interventions are lower than those of actual outbreaks. Nine papers focussed on the cost-effectiveness of dengue vaccines or dengue vector control; they do not provide any direct information on cost of dengue outbreaks, but their modelling methodologies could guide future research on cost-effectiveness of national surveillance systems.The country case studies--conducted in very different geographic and health system settings - unveiled rough estimates for 2011 outbreak costs of: 12 million US$ in Vietnam, 6.75 million US$ in Indonesia, 4.5 million US$ in Peru and 2.8 million US$ in Dominican Republic (all in 2012 US$). The proportions of the different cost components (vector control

Sensitivity and Specificity of the World Health Organization Dengue Classification Schemes for Severe Dengue Assessment in Children in Rio de Janeiro

PubMed Central

Macedo, Gleicy A.; Gonin, Michelle Luiza C.; Pone, Sheila M.; Cruz, Oswaldo G.; Nobre, Flávio F.; Brasil, Patrícia

2014-01-01

Background The clinical definition of severe dengue fever remains a challenge for researchers in hyperendemic areas like Brazil. The ability of the traditional (1997) as well as the revised (2009) World Health Organization (WHO) dengue case classification schemes to detect severe dengue cases was evaluated in 267 children admitted to hospital with laboratory-confirmed dengue. Principal Findings Using the traditional scheme, 28.5% of patients could not be assigned to any category, while the revised scheme categorized all patients. Intensive therapeutic interventions were used as the reference standard to evaluate the ability of both the traditional and revised schemes to detect severe dengue cases. Analyses of the classified cases (n = 183) demonstrated that the revised scheme had better sensitivity (86.8%, P<0.001), while the traditional scheme had better specificity (93.4%, P<0.001) for the detection of severe forms of dengue. Conclusions/Significance This improved sensitivity of the revised scheme allows for better case capture and increased ICU admission, which may aid pediatricians in avoiding deaths due to severe dengue among children, but, in turn, it may also result in the misclassification of the patients' condition as severe, reflected in the observed lower positive predictive value (61.6%, P<0.001) when compared with the traditional scheme (82.6%, P<0.001). The inclusion of unusual dengue manifestations in the revised scheme has not shifted the emphasis from the most important aspects of dengue disease and the major factors contributing to fatality in this study: shock with consequent organ dysfunction. PMID:24777054

Sensitivity and specificity of the World Health Organization dengue classification schemes for severe dengue assessment in children in Rio de Janeiro.

PubMed

Macedo, Gleicy A; Gonin, Michelle Luiza C; Pone, Sheila M; Cruz, Oswaldo G; Nobre, Flávio F; Brasil, Patrícia

2014-01-01

The clinical definition of severe dengue fever remains a challenge for researchers in hyperendemic areas like Brazil. The ability of the traditional (1997) as well as the revised (2009) World Health Organization (WHO) dengue case classification schemes to detect severe dengue cases was evaluated in 267 children admitted to hospital with laboratory-confirmed dengue. Using the traditional scheme, 28.5% of patients could not be assigned to any category, while the revised scheme categorized all patients. Intensive therapeutic interventions were used as the reference standard to evaluate the ability of both the traditional and revised schemes to detect severe dengue cases. Analyses of the classified cases (n = 183) demonstrated that the revised scheme had better sensitivity (86.8%, P<0.001), while the traditional scheme had better specificity (93.4%, P<0.001) for the detection of severe forms of dengue. This improved sensitivity of the revised scheme allows for better case capture and increased ICU admission, which may aid pediatricians in avoiding deaths due to severe dengue among children, but, in turn, it may also result in the misclassification of the patients' condition as severe, reflected in the observed lower positive predictive value (61.6%, P<0.001) when compared with the traditional scheme (82.6%, P<0.001). The inclusion of unusual dengue manifestations in the revised scheme has not shifted the emphasis from the most important aspects of dengue disease and the major factors contributing to fatality in this study: shock with consequent organ dysfunction.

Arterial hypertension and skin allergy are risk factors for progression from dengue to dengue hemorrhagic fever: a case control study.

PubMed

Teixeira, Maria Glória; Paixão, Enny S; Costa, Maria da Conceição N; Cunha, Rivaldo V; Pamplona, Luciano; Dias, Juarez P; Figueiredo, Camila A; Figueiredo, Maria Aparecida A; Blanton, Ronald; Morato, Vanessa; Barreto, Maurício L; Rodrigues, Laura C

2015-05-01

Currently, knowledge does not allow early prediction of which cases of dengue fever (DF) will progress to dengue hemorrhagic fever (DHF), to allow early intervention to prevent progression or to limit severity. The objective of this study is to investigate the hypothesis that some specific comorbidities increase the likelihood of a DF case progressing to DHF. A concurrent case-control study, conducted during dengue epidemics, from 2009 to 2012. Cases were patients with dengue fever that progressed to DHF, and controls were patients of dengue fever who did not progress to DHF. Logistic regression was used to estimate the association between DHF and comorbidities. There were 490 cases of DHF and 1,316 controls. Among adults, progression to DHF was associated with self-reported hypertension (OR = 1.6; 95% CI 1.1-2.1) and skin allergy (OR = 1.8; 95% CI 1.1-3.2) with DHF after adjusting for ethnicity and socio-economic variables. There was no statistically significant association between any chronic disease and progression to DHF in those younger than 15 years. Physicians attending patients with dengue fever should keep those with hypertension or skin allergies in health units to monitor progression for early intervention. This would reduce mortality by dengue.

Dengue Dynamics and Vaccine Cost-Effectiveness Analysis in the Philippines.

PubMed

Shim, Eunha

2016-11-02

Dengue is one of the most problematic vector-borne diseases in the Philippines, with an estimated 842,867 cases resulting in medical costs of $345 million U.S. dollars annually. In December 2015, the first dengue vaccine, known as chimeric yellow fever virus-dengue virus tetravalent dengue vaccine, was approved for use in the Philippines and is given to children 9 years of age. To estimate the cost-effectiveness of dengue vaccination in the Philippines, we developed an age-structured model of dengue transmission and vaccination. Using our model, we compared two vaccination scenarios entailing routine vaccination programs both with and without catch-up vaccination. Our results indicate that the higher the cost of vaccination, the less cost-effective the dengue vaccination program. With the current dengue vaccination program that vaccinates children 9 years of age, dengue vaccination is cost-effective for vaccination costs up to $70 from a health-care perspective and up to $75 from a societal perspective. Under a favorable scenario consisting of 1 year of catch-up vaccinations that target children 9-15 years of age, followed by regular vaccination of 9-year-old children, vaccination is cost-effective at costs up to $72 from a health-care perspective and up to $78 from a societal perspective. In general, dengue vaccination is expected to reduce the incidence of both dengue fever and dengue hemorrhagic fever /dengue shock syndrome. Our results demonstrate that even at relatively low vaccine efficacies, age-targeted vaccination may still be cost-effective provided the vaccination cost is sufficiently low. © The American Society of Tropical Medicine and Hygiene.

Economic Impact of Dengue Illness in the Americas

PubMed Central

Shepard, Donald S.; Coudeville, Laurent; Halasa, Yara A.; Zambrano, Betzana; Dayan, Gustavo H.

2011-01-01

The growing burden of dengue in endemic countries and outbreaks in previously unaffected countries stress the need to assess the economic impact of this disease. This paper synthesizes existing studies to calculate the economic burden of dengue illness in the Americas from a societal perspective. Major data sources include national case reporting data from 2000 to 2007, prospective cost of illness studies, and analyses quantifying underreporting in national routine surveillance systems. Dengue illness in the Americas was estimated to cost $2.1 billion per year on average (in 2010 US dollars), with a range of $1–4 billion in sensitivity analyses and substantial year to year variation. The results highlight the substantial economic burden from dengue in the Americas. The burden for dengue exceeds that from other viral illnesses, such as human papillomavirus (HPV) or rotavirus. Because this study does not include some components (e.g., vector control), it may still underestimate total economic consequences of dengue. PMID:21292885

Dengue-yellow fever sera cross-reactivity; challenges for diagnosis.

PubMed

Houghton-Triviño, Natalia; Montaña, Diana; Castellanos, Jaime

2008-01-01

The Flavivirus genera share epitopes inducing cross-reactive antibodies leading to great difficulty in differentially diagnosing flaviviral infections. This work was aimed at evaluating the complexity of dengue and yellow fever serological differential diagnosis. Dengue antibody capture ELISA and a yellow fever neutralisation test were carried out on 13 serum samples obtained from yellow fever patients, 20 acute serum samples from dengue patients and 19 voluntary serum samples pre- and post-vaccination with YF vaccine. Dengue ELISA revealed IgM reactivity in 46,2 % of yellow fever patients and 42 % of vaccinees. Sixteen out of 20 dengue patients (80 %) had high YF virus neutralisation titres. Such very high cross-reactivity data challenged differential laboratory diagnosis of dengue and yellow fever in areas where both flaviviruses co-circulate. New laboratory strategies are thus needed for improving the tests and providing a specific laboratory diagnosis. Cross-reactivity between Flaviviruses represents a great difficulty for epidemiological surveillance and preventing dengue, both of which demand urgent attention.

Host genetics and dengue fever.

PubMed

Xavier-Carvalho, Caroline; Cardoso, Cynthia Chester; de Souza Kehdy, Fernanda; Pacheco, Antonio Guilherme; Moraes, Milton Ozório

2017-12-01

Dengue is a major worldwide problem in tropical and subtropical areas; it is caused by four different viral serotypes, and it can manifest as asymptomatic, mild, or severe. Many factors interact to determine the severity of the disease, including the genetic profile of the infected patient. However, the mechanisms that lead to severe disease and eventually death have not been determined, and a great challenge is the early identification of patients who are more likely to progress to a worse health condition. Studies performed in regions with cyclic outbreaks such as Cuba, Brazil, and Colombia have demonstrated that African ancestry confers protection against severe dengue. Highlighting the host genetics as an important factor in infectious diseases, a large number of association studies between genetic polymorphisms and dengue outcomes have been published in the last two decades. The most widely used approach involves case-control studies with candidate genes, such as the HLA locus and genes for receptors, cytokines, and other immune mediators. Additionally, a Genome-Wide Association Study (GWAS) identified SNPs associated with African ethnicity that had not previously been identified in case-control studies. Despite the increasing number of publications in America, Africa, and Asia, the results are quite controversial, and a meta-analysis is needed to assess the consensus among the studies. SNPs in the MICB, TNF, CD209, FcγRIIA, TPSAB1, CLEC5A, IL10 and PLCE1 genes are associated with the risk or protection of severe dengue, and the findings have been replicated in different populations. A thorough understanding of the viral, human genetic, and immunological mechanisms of dengue and how they interact is essential for effectively preventing dengue, but also managing and treating patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Dengue fever

MedlinePlus

Clothing, mosquito repellent, and netting can help reduce the risk for mosquito bites that can spread dengue fever and other infections. Limit outdoor activity during mosquito season, especially when they ...

Dengue surveillance in the French armed forces: a dengue sentinel surveillance system in countries without efficient local epidemiological surveillance.

PubMed

de Laval, Franck; Dia, Aissata; Plumet, Sébastien; Decam, Christophe; Leparc Goffart, Isabelle; Deparis, Xavier

2013-01-01

Surveillance of travel-acquired dengue could improve dengue risk estimation in countries without ability. Surveillance in the French army in 2010 to 2011 highlighted 330 dengue cases, mainly in French West Indies and Guiana: DENV-1 circulated in Guadeloupe, Martinique, French Guiana, New Caledonia, Djibouti; DENV-3 in Mayotte and Djibouti; and DENV-4 in French Guiana. © 2012 International Society of Travel Medicine.

Guillain-Barre syndrome following dengue fever and literature review.

PubMed

Ralapanawa, Dissanayake Mudiyanselage Priyantha Udaya Kumara; Kularatne, Senanayake Abeysinghe Mudiyanselage; Jayalath, Widana Arachilage Thilak Ananda

2015-11-27

Dengue is an arboviral infection that classically presents with fever, joint pain, headaches, skin flush and morbilliform rashes. The incidence of neurological symptoms and complications in dengue varies from 1 to 25% that include encephalopathy, Guillain-Barre syndrome (GBS), acute motor weakness, seizures, neuritis, hypokalaemic paralysis, pyramidal tract signs, and a few more. Dengue fever as an antecedent infection in GBS is uncommon. A 34-years-old Sri Lankan Sinhalese male presented with fever, headache and myalgia of 3 days and developed leucopenia and thrombocytopenia without evidence of haemoconcentration. The diagnosis of dengue fever was confirmed as he had positive dengue NS1 antigen test on the third day of fever. He made full recovery and was discharged after 4 days of hospital stay. Six days later, he presented with history of acute flaccid weakness of both lower limbs and upper limbs which was of progressive ascending nature. The electromyography had evidence of demyelinating neuropathy and cerebrospinal fluid showed albuminocytological dissociation. Subsequently, IgM for dengue virus was positive. Dengue is endemic in Sri Lanka. Post dengue Guillain-Barre syndrome is a potential neurological complications of this infection.

Towards antiviral therapies for treating dengue virus infections.

PubMed

Kaptein, Suzanne Jf; Neyts, Johan

2016-10-01

Dengue virus is an emerging human pathogen that poses a huge public health burden by infecting annually about 390 million individuals of which a quarter report with clinical manifestations. Although progress has been made in understanding dengue pathogenesis, a licensed vaccine or antiviral therapy against this virus is still lacking. Treatment of patients is confined to symptomatic alleviation and supportive care. The development of dengue therapeutics thus remains of utmost importance. This review focuses on the few molecules that were evaluated in dengue virus-infected patients: balapiravir, chloroquine, lovastatin, prednisolone and celgosivir. The lessons learned from these clinical trials can be very helpful for the design of future trials for the next generation of dengue virus inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Priming effect of dengue and yellow fever vaccination on the immunogenicity, infectivity, and safety of a tetravalent dengue vaccine in humans.

PubMed

Qiao, Ming; Shaw, David; Forrat, Remi; Wartel-Tram, Anh; Lang, Jean

2011-10-01

A dengue vaccine effective against all four serotypes is urgently needed. However, safety and immunogenicity could be affected by prior exposure to flaviviruses. This open, controlled, phase IIa study was conducted in 35 healthy adults who had received monovalent, live attenuated Vero cell-derived dengue vaccine against dengue virus 1 (VDV1) or 2 (VDV2) or yellow fever (YF) vaccine 1 year before or who were flavivirus-naïve. All participants received one subcutaneous injection of tetravalent dengue vaccine (TDV) and were followed for 180 days. Previous vaccination did not increase reactogenicity, laboratory abnormalities, or incidence of vaccine viremia, but it did increase the neutralizing antibody response to dengue virus that persisted at day 180. There was no increase in YF antibodies in participants previously immunized with YF vaccine. Prior exposure to YF or monovalent dengue vaccines had no adverse effects on the safety or incidence of viremia associated with this TDV, but it increased immunogenicity.

The 2012 dengue outbreak in Madeira: exploring the origins.

PubMed

Wilder-Smith, A; Quam, M; Sessions, O; Rocklov, J; Liu-Helmersson, J; Franco, L; Khan, K

2014-02-27

In 2012, Madeira reported its first major outbreak of dengue. To identify the origin of the imported dengue virus, we investigated the interconnectivity via air travel between dengue-endemic countries and Madeira, and compared available sequences against GenBank. There were 22,948 air travellers to Madeira in 2012, originating from twenty-nine dengue-endemic countries; 89.6% of these international travellers originated from Venezuela and Brazil. We developed an importation index that takes into account both travel volume and the extent of dengue incidence in the country of origin. Venezuela and Brazil had by far the highest importation indices compared with all other dengue-endemic countries. The importation index for Venezuela was twice as high as that for Brazil. When taking into account seasonality in the months preceding the onset of the Madeira outbreak, this index was even seven times higher for Venezuela than for Brazil during this time. Dengue sequencing shows that the virus responsible for the Madeira outbreak was most closely related to viruses circulating in Venezuela, Brazil and Columbia. Applying the importation index, Venezuela was identified as the most likely origin of importation of dengue virus via travellers to Madeira. We propose that the importation index is a new additional tool that can help to identify and anticipate the most probable country of origin for importation of dengue into currently non-endemic countries.

Human Immune Responses to Dengue Viruses.

DTIC Science & Technology

1984-08-01

ND-R171 381 HUR IMMUNE RESPONSES TO DENGUE VIRUSES (U) 1/1 MASSRCHUSETTS UNIY M9DICAL SCHOOL WORCESTER F R~ ENNIS RUG 94 DRMt17-2-C-2233 UNCLASSIFIED...Responses to Dengue Viruses Annual Report 0(August 1983-July 1984) Francis A. Ennis, M.D. August 1984 Supported by U.S. Army Medical Research and...3M1- NO. SON No. Frederick, Maryland 21701-5012 61102A 61102BSI0 AA 104 11. TITLE Oxkf* Samqy Oao" Human Immune Responses to Dengue Viruses 12. PERSON

An innovative forecasting and dashboard system for Malaysian dengue trends

NASA Astrophysics Data System (ADS)

Jamil, Jastini Mohd; Shaharanee, Izwan Nizal Mohd

2016-08-01

Dengue fever has been recognized in over 100 countries and 2.5 billion people live in areas where dengue is endemic. It is currently a serious arthropod-borne disease, affecting around 50-100 million people worldwide every year. Dengue fever is also prevalent in Malaysia with numerous cases including mortality recorded over the past year. In 2012, a total of 21,900 cases of dengue fever were reported with 35 deaths. Dengue, a mosquito-transmitted virus, causes a high fever accompanied by significant pain in afflicted patient and the Aedes Aegypti mosquito is the primary disease carrier. Knowing the dangerous effect of dengue fever, thus one of the solutions is to implement an innovative forecasting and dashboard system of dengue spread in Malaysia, with emphasize on an early prediction of dengue outbreak. Specifically, the model developed will provide with a valuable insight into strategically managing and controlling the future dengue epidemic. Importantly, this research will deliver the message to health policy makers such as The Ministry of Health Malaysia (MOH), practitioners, and researchers of the importance to integrate their collaboration in exploring the potential strategies in order to reduce the future burden of the increase in dengue transmission cases in Malaysia.

Clinico-laboratory spectrum of dengue viral infection and risk factors associated with dengue hemorrhagic fever: a retrospective study.

PubMed

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

2015-09-30

The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease. A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period of six years (2008 - 2013) was performed. Patient's demographics, clinical and laboratory findings were recorded via structured data collection form. Patients were categorized into dengue fever (DF) and dengue hemorrhagic fever (DHF). Appropriate statistical methods were used to compare these two groups in order to determine difference in clinico-laboratory characteristics and to identify independent risk factors of DHF. A total 667 dengue patients (30.69 ± 16.13 years; Male: 56.7 %) were reviewed. Typical manifestations of dengue like fever, myalgia, arthralgia, headache, vomiting, abdominal pain and skin rash were observed in more than 40 % patients. DHF was observed in 79 (11.8 %) cases. Skin rash, dehydration, shortness of breath, pleural effusion and thick gall bladder were more significantly (P < 0.05) associated with DHF than DF. Multivariate regression analysis demonstrated presence of age > 40 years (OR: 4.1, P < 0.001), secondary infection (OR: 2.7, P = 0.042), diabetes mellitus (OR: 2.8, P = 0.041), lethargy (OR: 3.1, P = 0.005), thick gallbladder (OR: 1.7, P = 0.029) and delayed hospitalization (OR: 2.3, P = 0.037) as independent predictors of DHF. Overall mortality was 1.2 % in our study. Current study demonstrated that DF and DHF present significantly different clinico-laboratory profile. Older age, secondary infection, diabetes mellitus, lethargy, thick gallbladder and delayed hospitalization significantly predict DHF. Prior knowledge of expected

Epidemiological Characteristics and Risk Factors of Dengue Infection in Korean Travelers

PubMed Central

2016-01-01

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

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.

The maximum potential market for dengue drugs V 1.0.

PubMed

Dow, Geoffrey; Mora, Eric

2012-11-01

Drugs offer a complementary approach to vaccines for preventing the progression of symptoms and onset of the severe manifestations of dengue. Despite the rapid maturation of the research and development infrastructure for dengue drugs and the increasing frequency of dengue inhibitors reported in the scientific literature, the potential size of the market for dengue drugs has not been articulated. In the present work, extrapolating from publicly available information, we explored the economic burden attributable to dengue, the impact of dengue vaccines on clinical case loads, a possible alternative to tiered pricing for products for neglected diseases, and defined the maximum potential market for a dengue drug. Our projections suggest that in 2006, the annual global burden of dengue was US $1.7billion. Our proposed alternative to existing tiered pricing structures is that during a temporary period of market exclusivity, individual countries would pay 50% of the per-case equivalent of economic costs saved through the use of a dengue drug. This would yield prices per case of US $13-$239 depending on drug effectiveness and cost of medical and indirect costs and lost productivity in different countries. Assuming that such a pricing scheme was embraced, the maximum potential market for a dengue drug or drugs that on average reduced 40% of economic costs might be as high as US $338million annually. Our simulations suggest that dengue vaccines will begin to reduce the clinical case load of dengue in 2022, but that the number of cases will not decrease below 2006 levels and the proportion vaccinated will remain well below that required for the onset of herd immunity during the period of market exclusivity after the licensure of the first wave of dengue drugs. Copyright © 2012 Elsevier B.V. All rights reserved.

Dengue outbreak in Key West, Florida, USA, 2009.

PubMed

Radke, Elizabeth G; Gregory, Christopher J; Kintziger, Kristina W; Sauber-Schatz, Erin K; Hunsperger, Elizabeth A; Gallagher, Glen R; Barber, Jean M; Biggerstaff, Brad J; Stanek, Danielle R; Tomashek, Kay M; Blackmore, Carina G M

2012-01-01

After 3 dengue cases were acquired in Key West, Florida, we conducted a serosurvey to determine the scope of the outbreak. Thirteen residents showed recent infection (infection rate 5%; 90% CI 2%-8%), demonstrating the reemergence of dengue in Florida. Increased awareness of dengue among health care providers is needed.

Assessing weather effects on dengue disease in Malaysia.

PubMed

Cheong, Yoon Ling; Burkart, Katrin; Leitão, Pedro J; Lakes, Tobia

2013-11-26

The number of dengue cases has been increasing on a global level in recent years, and particularly so in Malaysia, yet little is known about the effects of weather for identifying the short-term risk of dengue for the population. The aim of this paper is to estimate the weather effects on dengue disease accounting for non-linear temporal effects in Selangor, Kuala Lumpur and Putrajaya, Malaysia, from 2008 to 2010. We selected the weather parameters with a Poisson generalized additive model, and then assessed the effects of minimum temperature, bi-weekly accumulated rainfall and wind speed on dengue cases using a distributed non-linear lag model while adjusting for trend, day-of-week and week of the year. We found that the relative risk of dengue cases is positively associated with increased minimum temperature at a cumulative percentage change of 11.92% (95% CI: 4.41-32.19), from 25.4 °C to 26.5 °C, with the highest effect delayed by 51 days. Increasing bi-weekly accumulated rainfall had a positively strong effect on dengue cases at a cumulative percentage change of 21.45% (95% CI: 8.96, 51.37), from 215 mm to 302 mm, with the highest effect delayed by 26-28 days. The wind speed is negatively associated with dengue cases. The estimated lagged effects can be adapted in the dengue early warning system to assist in vector control and prevention plan.

Assessing Weather Effects on Dengue Disease in Malaysia

PubMed Central

Cheong, Yoon Ling; Burkart, Katrin; Leitão, Pedro J.; Lakes, Tobia

2013-01-01

The number of dengue cases has been increasing on a global level in recent years, and particularly so in Malaysia, yet little is known about the effects of weather for identifying the short-term risk of dengue for the population. The aim of this paper is to estimate the weather effects on dengue disease accounting for non-linear temporal effects in Selangor, Kuala Lumpur and Putrajaya, Malaysia, from 2008 to 2010. We selected the weather parameters with a Poisson generalized additive model, and then assessed the effects of minimum temperature, bi-weekly accumulated rainfall and wind speed on dengue cases using a distributed non-linear lag model while adjusting for trend, day-of-week and week of the year. We found that the relative risk of dengue cases is positively associated with increased minimum temperature at a cumulative percentage change of 11.92% (95% CI: 4.41–32.19), from 25.4 °C to 26.5 °C, with the highest effect delayed by 51 days. Increasing bi-weekly accumulated rainfall had a positively strong effect on dengue cases at a cumulative percentage change of 21.45% (95% CI: 8.96, 51.37), from 215 mm to 302 mm, with the highest effect delayed by 26–28 days. The wind speed is negatively associated with dengue cases. The estimated lagged effects can be adapted in the dengue early warning system to assist in vector control and prevention plan. PMID:24287855

Towards a climate-driven dengue decision support system for Thailand

NASA Astrophysics Data System (ADS)

Lowe, Rachel; Cazelles, Bernard; Paul, Richard; Rodó, Xavier

2014-05-01

Dengue is a peri-urban mosquito-transmitted disease, ubiquitous in the tropics and the subtropics. The geographic distribution of dengue and its more severe form, dengue haemorrhagic fever (DHF), have expanded dramatically in the last decades and dengue is now considered to be the world's most important arboviral disease. Recent demographic changes have greatly contributed to the acceleration and spread of the disease along with uncontrolled urbanization, population growth and increased air travel, which acts as a mechanism for transporting and exchanging dengue viruses between endemic and epidemic populations. The dengue vector and virus are extremely sensitive to environmental conditions such as temperature, humidity and precipitation that influence mosquito biology, abundance and habitat and the virus replication speed. In order to control the spread of dengue and impede epidemics, decision support systems are required that take into account the multi-faceted array of factors that contribute to increased dengue risk. Due to availability of seasonal climate forecasts, that predict the average climate conditions for forthcoming months/seasons in both time and space, there is an opportunity to incorporate precursory climate information in a dengue decision support system to aid epidemic planning months in advance. Furthermore, oceanic indicators from teleconnected areas in the Pacific and Indian Ocean, that can provide some indication of the likely prevailing climate conditions in certain regions, could potentially extend predictive lead time in a dengue early warning system. In this paper we adopt a spatio-temporal Bayesian modelling framework for dengue in Thailand to support public health decision making. Monthly cases of dengue in the 76 provinces of Thailand for the period 1982-2012 are modelled using a multi-layered approach. Environmental explanatory variables at various spatial and temporal resolutions are incorporated into a hierarchical model in order to

Cost of dengue outbreaks: literature review and country case studies

PubMed Central

2013-01-01

Background Dengue disease surveillance and vector surveillance are presumed to detect dengue outbreaks at an early stage and to save – through early response activities – resources, and reduce the social and economic impact of outbreaks on individuals, health systems and economies. The aim of this study is to unveil evidence on the cost of dengue outbreaks. Methods Economic evidence on dengue outbreaks was gathered by conducting a literature review and collecting information on the costs of recent dengue outbreaks in 4 countries: Peru, Dominican Republic, Vietnam, and Indonesia. The literature review distinguished between costs of dengue illness including cost of dengue outbreaks, cost of interventions and cost-effectiveness of interventions. Results Seventeen publications on cost of dengue showed a large range of costs from 0.2 Million US$ in Venezuela to 135.2 Million US$ in Brazil. However, these figures were not standardized to make them comparable. Furthermore, dengue outbreak costs are calculated differently across the publications, and cost of dengue illness is used interchangeably with cost of dengue outbreaks. Only one paper from Australia analysed the resources saved through active dengue surveillance. Costs of vector control interventions have been reported in 4 studies, indicating that the costs of such interventions are lower than those of actual outbreaks. Nine papers focussed on the cost-effectiveness of dengue vaccines or dengue vector control; they do not provide any direct information on cost of dengue outbreaks, but their modelling methodologies could guide future research on cost-effectiveness of national surveillance systems. The country case studies – conducted in very different geographic and health system settings - unveiled rough estimates for 2011 outbreak costs of: 12 million US$ in Vietnam, 6.75 million US$ in Indonesia, 4.5 million US$ in Peru and 2.8 million US$ in Dominican Republic (all in 2012 US$). The proportions of the

International Dengue Vaccine Communication and Advocacy: Challenges and Way Forward.

PubMed

Carvalho, Ana; Van Roy, Rebecca; Andrus, Jon

2016-01-01

Dengue vaccine introduction will likely occur soon. However, little has been published on international dengue vaccine communication and advocacy. More effort at the international level is required to review, unify and strategically disseminate dengue vaccine knowledge to endemic countries' decision makers and potential donors. Waiting to plan for the introduction of new vaccines until licensure may delay access in developing countries. Concerted efforts to communicate and advocate for vaccines prior to licensure are likely challenged by unknowns of the use of dengue vaccines and the disease, including uncertainties of vaccine impact, vaccine access and dengue's complex pathogenesis and epidemiology. Nevertheless, the international community has the opportunity to apply previous best practices for vaccine communication and advocacy. The following key strategies will strengthen international dengue vaccine communication and advocacy: consolidating existing coalitions under one strategic umbrella, urgently convening stakeholders to formulate the roadmap for integrated dengue prevention and control, and improving the dissemination of dengue scientific knowledge.

Four Cases of Autochthonous Dengue Infection in Japan and 46 Imported Cases: Characteristics of Japanese Dengue.

PubMed

Yoshimura, Yukihiro; Sakamoto, Yohei; Amano, Yuichiro; Nakaharai, Kazuhiko; Yaita, Kenichiro; Hoshina, Tokio; Kurai, Hanako; Usuku, Shuzo; Tachikawa, Natsuo

2015-01-01

A dengue outbreak occurred in Japan 2014. We investigated the characteristics of dengue infection among Japanese. We investigated the medical charts retrospectively. Patients The study participants are patients who came to our clinic between 2008 and 2014. We investigated 4 domestic cases and 46 imported cases of Japanese with laboratory confirmation of dengue. Major symptoms were fever (100%), rash (86%), fatigue (84%), headache (81%), joint pain (66%), muscle pain (49%), and bleeding (6%). A late rash that appeared near the time of fever resolution was observed in 37 cases (74%). A total of 38/43 (88%) cases had low WBC count (<3,500 /μL) during the febrile period, 42/48 (88%) cases had a low platelet (PLT) count (<130×10(3)/μL), and 44/50 (88%) cases had a C-reactive protein (CRP) <2.0 mg/dL. Patients with a high fever, late rash, fever-associated leukopenia, low PLT count, low CRP, and elevated aminotransferases are generally suspected of having a dengue infection.

Diabetes mellitus increases severity of thrombocytopenia in dengue-infected patients.

PubMed

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

2015-02-10

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. 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. 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 dengue patients. Dengue patients with diabetes tended to have more severe

Molecular epidemiology and evolutionary analysis of dengue virus type 2, circulating in Delhi, India.

PubMed

Sharma, Pankaj; Mittal, Veena; Chhabra, Mala; Kumari, Roop; Singh, Priyanka; Venkatesh, Srinivas

2016-12-01

Dengue virus type 2 (DENV-2) has been associated with severe dengue outbreaks in many countries including India. Its predominance was recorded nearly after a decade in the capital city, Delhi in 2013. The present study characterizes DENV-2 circulated during 2013-2014. Analysis based on envelope (E) gene showed the presence of two clades (I and II) of DENV-2, within the Cosmopolitan genotype. Analysis of time of most recent common ancestor revealed the existence of clade I for more than a decade (95 % HPD 13-16 years) however, clade II showed comparatively recent emergence (95 % HPD 5-13 years). Presence of different clades is of high significance as this may result in increased virus transmission and major outbreaks. Further, the presence of a unique amino acid substitution, Q325H was also observed in an isolate; 14/D2/Del/2013 (KT717981). This substitution falls in immune epitope (epitope id: 150268) and may have important role in host immune response.

Dengue Outbreak in Key West, Florida, USA, 2009

PubMed Central

Radke, Elizabeth G.; Gregory, Christopher J.; Kintziger, Kristina W.; Sauber-Schatz, Erin K.; Hunsperger, Elizabeth A.; Gallagher, Glen R.; Barber, Jean M.; Biggerstaff, Brad J.; Stanek, Danielle R.; Tomashek, Kay M.

2012-01-01

After 3 dengue cases were acquired in Key West, Florida, we conducted a serosurvey to determine the scope of the outbreak. Thirteen residents showed recent infection (infection rate 5%; 90% CI 2%–8%), demonstrating the reemergence of dengue in Florida. Increased awareness of dengue among health care providers is needed. PMID:22257471

Economic and disease burden of dengue in Mexico.

PubMed

Undurraga, Eduardo A; Betancourt-Cravioto, Miguel; Ramos-Castañeda, José; Martínez-Vega, Ruth; Méndez-Galván, Jorge; Gubler, Duane J; Guzmán, María G; Halstead, Scott B; Harris, Eva; Kuri-Morales, Pablo; Tapia-Conyer, Roberto; Shepard, Donald S

2015-03-01

Dengue imposes a substantial economic and disease burden in most tropical and subtropical countries. Dengue incidence and severity have dramatically increased in Mexico during the past decades. Having objective and comparable estimates of the economic burden of dengue is essential to inform health policy, increase disease awareness, and assess the impact of dengue prevention and control technologies. We estimated the annual economic and disease burden of dengue in Mexico for the years 2010-2011. We merged multiple data sources, including a prospective cohort study; patient interviews and macro-costing from major hospitals; surveillance, budget, and health data from the Ministry of Health; WHO cost estimates; and available literature. We conducted a probabilistic sensitivity analysis using Monte Carlo simulations to derive 95% certainty levels (CL) for our estimates. Results suggest that Mexico had about 139,000 (95%CL: 128,000-253,000) symptomatic and 119 (95%CL: 75-171) fatal dengue episodes annually on average (2010-2011), compared to an average of 30,941 symptomatic and 59 fatal dengue episodes reported. The annual cost, including surveillance and vector control, was US$170 (95%CL: 151-292) million, or $1.56 (95%CL: 1.38-2.68) per capita, comparable to other countries in the region. Of this, $87 (95%CL: 87-209) million or $0.80 per capita (95%CL: 0.62-1.12) corresponds to illness. Annual disease burden averaged 65 (95%CL: 36-99) disability-adjusted life years (DALYs) per million population. Inclusion of long-term sequelae, co-morbidities, impact on tourism, and health system disruption during outbreaks would further increase estimated economic and disease burden. With this study, Mexico joins Panama, Puerto Rico, Nicaragua, and Thailand as the only countries or areas worldwide with comprehensive (illness and preventive) empirical estimates of dengue burden. Burden varies annually; during an outbreak, dengue burden may be significantly higher than that of the pre

Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Challenges of a Dengue Vaccine.

PubMed

Screaton, Gavin; Mongkolsapaya, Juthathip

2017-07-17

A dengue vaccine has been pursued for more than 50 years and, unlike other flaviviral vaccines such as that against yellow fever, progress has been slow. In this review, we describe progress toward the first licensed dengue vaccine Dengvaxia, which does not give complete protection against disease. The antibody response to the dengue virion is reviewed, highlighting immunodominant yet poorly neutralizing responses in the context of a highly dynamic structurally flexible dengue virus particle. Finally, we review recent evidence for cross-reactivity between antibody responses to Zika and dengue viruses, which may further complicate the development of broadly protective dengue virus vaccines. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Discovery and characterization of potential prognostic biomarkers for dengue hemorrhagic fever.

PubMed

Poole-Smith, B Katherine; Gilbert, Alexa; Gonzalez, Andrea L; Beltran, Manuela; Tomashek, Kay M; Ward, Brian J; Hunsperger, Elizabeth A; Ndao, Momar

2014-12-01

Half a million patients are hospitalized with severe dengue every year, many of whom would die without timely, appropriate clinical intervention. The majority of dengue cases are uncomplicated; however, 2-5% progress to severe dengue. Severe dengue cases have been reported with increasing frequency over the last 30 years. To discover biomarkers for severe dengue, we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze dengue virus positive serum samples from the acute phase of infection. Using this method, 16 proteins were identified as candidate biomarkers for severe dengue. From these 16 biomarkers, three candidates were selected for confirmation by enzyme-linked immunosorbent assay and Western blot: vitronectin (Vtn, 55.1 kDa), hemopexin (Hx, 52.4 kDa), and serotransferrin (Tf, 79.2 kDa). Vitronectin, Hx, and Tf best differentiated between dengue and severe dengue. © The American Society of Tropical Medicine and Hygiene.

Discovery and Characterization of Potential Prognostic Biomarkers for Dengue Hemorrhagic Fever

PubMed Central

Poole-Smith, B. Katherine; Gilbert, Alexa; Gonzalez, Andrea L.; Beltran, Manuela; Tomashek, Kay M.; Ward, Brian J.; Hunsperger, Elizabeth A.; Ndao, Momar

2014-01-01

Half a million patients are hospitalized with severe dengue every year, many of whom would die without timely, appropriate clinical intervention. The majority of dengue cases are uncomplicated; however, 2–5% progress to severe dengue. Severe dengue cases have been reported with increasing frequency over the last 30 years. To discover biomarkers for severe dengue, we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze dengue virus positive serum samples from the acute phase of infection. Using this method, 16 proteins were identified as candidate biomarkers for severe dengue. From these 16 biomarkers, three candidates were selected for confirmation by enzyme-linked immunosorbent assay and Western blot: vitronectin (Vtn, 55.1 kDa), hemopexin (Hx, 52.4 kDa), and serotransferrin (Tf, 79.2 kDa). Vitronectin, Hx, and Tf best differentiated between dengue and severe dengue. PMID:25349378

Developing a Social Autopsy Tool for Dengue Mortality: A Pilot Study

PubMed Central

Arauz, María José; Ridde, Valéry; Hernández, Libia Milena; Charris, Yaneth; Carabali, Mabel; Villar, Luis Ángel

2015-01-01

Background Dengue fever is a public health problem in the tropical and sub-tropical world. Dengue cases have grown dramatically in recent years as well as dengue mortality. Colombia has experienced periodic dengue outbreaks with numerous dengue related-deaths, where the Santander department has been particularly affected. Although social determinants of health (SDH) shape health outcomes, including mortality, it is not yet understood how these affect dengue mortality. The aim of this pilot study was to develop and pre-test a social autopsy (SA) tool for dengue mortality. Methods and Findings The tool was developed and pre-tested in three steps. First, dengue fatal cases and ‘near misses’ (those who recovered from dengue complications) definitions were elaborated. Second, a conceptual framework on determinants of dengue mortality was developed to guide the construction of the tool. Lastly, the tool was designed and pre-tested among three relatives of fatal cases and six near misses in 2013 in the metropolitan zone of Bucaramanga. The tool turned out to be practical in the context of dengue mortality in Colombia after some modifications. The tool aims to study the social, individual, and health systems determinants of dengue mortality. The tool is focused on studying the socioeconomic position and the intermediary SDH rather than the socioeconomic and political context. Conclusions The SA tool is based on the scientific literature, a validated conceptual framework, researchers’ and health professionals’ expertise, and a pilot study. It is the first time that a SA tool has been created for the dengue mortality context. Our work furthers the study on SDH and how these are applied to neglected tropical diseases, like dengue. This tool could be integrated in surveillance systems to provide complementary information on the modifiable and avoidable death-related factors and therefore, be able to formulate interventions for dengue mortality reduction. PMID:25658485

The Epidemiological Characteristics and Dynamic Transmission of Dengue in China, 2013

PubMed Central

lu, Liang; Bi, Peng; Lv, Ming; Liu, Qiyong

2016-01-01

Background There was a dengue epidemic in several regions of China in 2013. No study has explored the dynamics of dengue transmission between different geographical locations with dengue outbreaks in China. The purpose of the study is to analyze the epidemiological characteristics and to explore the dynamic transmission of dengue in China, 2013. Methodology and Principal Findings Records of dengue cases of 2013 were obtained from the China Notifiable Disease Surveillance System. Full E-gene sequences of dengue virus detected from the outbreak regions of China were download from GenBank. Geographical Information System and heatmaps were used to describe the epidemiological characteristics. Maximum Likelihood phylogenetic and Bayesian phylogeographic analyses were conducted to explore the dengue dynamic transmission. Yunnan Province and Guangdong Province had the highest imported cases in the 2013 epidemic. In the locations with local dengue transmission, most of imported cases occurred from June to November 2013 while local dengue cases developed from July to December, 2013. There were significant variations for the incidences of dengue, in terms of age distributions, among different geographic locations. However, gender differences were identified in Guangzhou, Foshan and Xishuangbanna. DENV 1–3 were detected in all locations with the disease outbreaks. Some genotypes were detected in more than one locations and more than one genotypes have been detected in several locations. The dengue viruses introduced to outbreak areas were predominantly from Southeast Asia. In Guangdong Province, the phylogeographical results indicated that dengue viruses of DENV 1 were transmitted to neighboring cities Foshan and Zhongshan from Guangzhou city, and then transmitted to Jiangmen city. The virus in DENV 3 was introduced to Guangzhou city, Guangdong Province from Xishuangbanna prefecture, Yunnan Province. Conclusions Repeated dengue virus introductions from Southeast Asia and

Association between sex, nutritional status, severity of dengue hemorrhagic fever, and immune status in infants with dengue hemorrhagic fever.

PubMed

Nguyen, Thanh Hung; Nguyen, Trong Lan; Lei, Huan-Yao; Lin, Yee-Shin; Le, Bich Lien; Huang, Kao-Jean; Lin, Chiou-Feng; Do, Quang Ha; Vu, Thi Que Huong; Lam, Thi My; Yeh, Trai-Ming; Huang, Jyh-Hsiung; Liu, Ching-Chuan; Halstead, Scott B

2005-04-01

The association between sex, nutritional status, and the severity of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), and immune status was investigated in 245 Vietnamese infants with predominantly primary infections with dengue virus. Male and female infants were at equal risk of developing DHF/DSS. However, infants of low height and weight for age were under-represented among DHF/DSS cases compared with 533 healthy baby clinic infant controls. Acute illness phase blood levels of selected cytokines (interferon-gamma and tumor necrosis factor-alpha) and serum levels of antibodies to dengue virus were elevated in the same range in male and female infants with DHF/DSS, as well as in infants with and without malnutrition.

Forecast of dengue incidence using temperature and rainfall.

PubMed

Hii, Yien Ling; Zhu, Huaiping; Ng, Nawi; Ng, Lee Ching; Rocklöv, Joacim

2012-01-01

An accurate early warning system to predict impending epidemics enhances the effectiveness of preventive measures against dengue fever. The aim of this study was to develop and validate a forecasting model that could predict dengue cases and provide timely early warning in Singapore. We developed a time series Poisson multivariate regression model using weekly mean temperature and cumulative rainfall over the period 2000-2010. Weather data were modeled using piecewise linear spline functions. We analyzed various lag times between dengue and weather variables to identify the optimal dengue forecasting period. Autoregression, seasonality and trend were considered in the model. We validated the model by forecasting dengue cases for week 1 of 2011 up to week 16 of 2012 using weather data alone. Model selection and validation were based on Akaike's Information Criterion, standardized Root Mean Square Error, and residuals diagnoses. A Receiver Operating Characteristics curve was used to analyze the sensitivity of the forecast of epidemics. The optimal period for dengue forecast was 16 weeks. Our model forecasted correctly with errors of 0.3 and 0.32 of the standard deviation of reported cases during the model training and validation periods, respectively. It was sensitive enough to distinguish between outbreak and non-outbreak to a 96% (CI = 93-98%) in 2004-2010 and 98% (CI = 95%-100%) in 2011. The model predicted the outbreak in 2011 accurately with less than 3% possibility of false alarm. We have developed a weather-based dengue forecasting model that allows warning 16 weeks in advance of dengue epidemics with high sensitivity and specificity. We demonstrate that models using temperature and rainfall could be simple, precise, and low cost tools for dengue forecasting which could be used to enhance decision making on the timing, scale of vector control operations, and utilization of limited resources.

Clinical course of dengue in patients with thalassaemia.

PubMed

Natesirinilkul, Rungrote; Tantiworawit, Adisak; Charoenkwan, Pimlak

2013-02-01

Dengue and thalassaemia are prevalent in tropical regions. Thalassaemia patients with dengue present with atypical clinical manifestations and may experience more severe disease and complications. To investigate the clinical manifestations and outcome in thalassaemia patients with dengue. Medical records of thalassaemia patients aged from birth to 18 years with serologically-confirmed dengue who were admitted to Chiang Mai University Hospital, Thailand from January 2005 to December 2010 were reviewed retrospectively. Clinical presentation, laboratory results and outcome were analysed. Twenty patients were included and their mean (SD) age was 13·6 (3·1) years. Patients were as follows: haemoglobin H (HbH)/Hb Constant Spring disease 7, HbH disease 3, HbH disease/HbE trait one, beta-thalassaemia/HbE disease 7, beta-thalassaemia/HbS disease one and unspecified thalassaemia one. Four patients had primary and the others secondary dengue. Five patients (25%) had severe dengue, three with severe liver involvement, one with a massive upper gastro-intestinal haemorrhage and one with acute interstitial nephritis, raised creatinine and seizures. Nineteen patients required red cells transfusions. All made a full recovery. Almost all patients presented with haemoglobin lower than baseline. While mean (SD) haemoglobin at baseline was 8·2 (1·6) g/dl, mean (SD) haemoglobin on admission was 6·4 (1·6) g/dl. Median maximum AST and ALT levels were 359 (range 42-5344) and 81 (12-1846) units/L, respectively. Thalassaemia patients with dengue present with anaemia rather than haemoconcentration. Most patients have markedly increased AST levels in relation to ALT, and severe dengue, especially severe liver involvement, is common. In patients with thalassaemia, awareness of the atypical manifestations should aid early recognition of dengue.

Evolving herbal formulations in management of dengue fever.

PubMed

Singh, Pawan Kumar; Rawat, Pooja

Dengue is endemic in more than 100 countries and it is estimated that annually above 390 million infections occur globally. During the period between 1996-2015, a massive increase of more than 500 per cent has been recorded in number of dengue cases reported in India. Till date, there are no specific globally accepted treatments for dengue fever in any system of medicine. Dengue does not cause very high mortality if properly handled and is currently being managed by clinicians through various adjuvant and alternative therapeutic options. Various plant based preparations have been used in different parts of India for combating dengue and are simultaneously also being scientifically validated by researchers. However, number of such scientific validation studies on phytomedicines are very less in India. Out of twenty-two plants reported against dengue, only four have been studied scientifically. Azadirachta indica, Carica papaya, Hippophae rhamnoides and Cissampelos pareira extracts were found effective and demonstrated improvement in clinical symptoms and direct inhibitory effect on dengue virus. C. papaya clinical trial showed increase in platelet count and faster recovery. These plants may be explored further as probable candidates for drug discovery against dengue. There is a need to search more such herbal formulations, which are being practiced at local level, document properly and validate them scientifically to confirm efficacy, mechanistic action and safety, before use. The herbal formulations being used by communities are the low hanging fruits which may provide alternative or adjuvant therapy if proper validation, value addition and product development steps are followed. This paper aims to review the recent status of dengue cases, deaths and evolving curative herbal solutions adapted and reported from India to combat the disease. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights

[Dengue fever--not just a tropical infectious disease].

PubMed

Stock, Ingo

2016-03-01

Dengue fever is a viral disease that is transmitted primarily by Aedes mosquitoes, i. e., A. aegypti and A. albopictus. Other species are rarely involved. The disease is caused by dengue virus, an enveloped RNA virus which belongs to the family of flaviviridae. Although most infections are asymptomatic, in 20 to 30 percentages all cases infections are accompanied with high fever and other influenza-like signs of illness. Serious medical conditions with lethal complications also occur. During the last decades, the incidence of dengue fever rose sharply in many tropical and subtropical countries. In some of these regions, dengue is one of the leading causes of death in children. In Europe, since a few years a strong clustering of dengue fever cases has been registered in travelers returning from certain tropical or subtropical regions. Recently, autochthonous outbreaks have been observed on the Atlantic island of Madeira and in a few other regions of South Europe. Treatment of dengue fever is supportive and symptomatic, a specific therapy does not exist. For prevention of disease, vector control is of crucial importance.

Drugs for dengue: a patent review (2010-2014).

PubMed

Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam

2014-11-01

Almost half the global population is estimated to be at risk of contracting dengue infection. Of the 400 million infections estimated to occur annually, 4 million can be potentially life-threatening leading to vascular leakage and shock. The only treatment available to severe dengue patients is fluid replacement therapy and supportive care. A drug for treating dengue is an urgent need. This article endeavors to provide an overview of the experimental dengue drugs being developed around the world as reflected in the recent patent literature spanning the last few years (2010-2014). Dengue drug development is essentially in its infancy and currently hobbled by multiple factors including a poor understanding of the molecular mechanism of severe disease and lack of reliable small animal model for preclinical drug evaluation. More intense R&D coupled to setting up product development partnerships to facilitate the efficient movement of a drug molecule from the laboratory to the clinic is needed to make antiviral therapy for dengue a reality in the coming future.

Age-specific seroprevalence of dengue infection in Hong Kong.

PubMed

Lee, Polly; Yeung, Apple C M; Chen, Zigui; Chan, Martin C W; Sze, Kin Ho; Chan, Paul K S

2018-05-02

A newly developed dengue virus vaccine (chimeric yellow fever virus-tetravalent dengue vaccine [CYD-TDV]) has recently been licensed for clinical use. The World Health Organization recommends vaccination for populations with seroprevalence of at least 70% to maximize public health impact. This study aimed to delineate the seroprevalence of dengue infection in Hong Kong. A total of 105 972 serum samples submitted for clinical testing during the period 2013-2015 were age-stratified and sex-stratified. For each year of collection, 25 samples were randomly selected from each age-sex group. Altogether, 2100 samples were tested for the dengue immunoglobulin G (IgG) antibody using a non-type-specific ELISA kit. The overall dengue IgG-positive rate was 4.6% and showed no significant change over the 3 years. The positive rate was not associated with sex, but a steep rise in seroprevalence for persons above 65 years (32.7%) was observed. The low dengue seroprevalence in Hong Kong does not support implementation of a national immunization program. Majority of the population in Hong Kong are susceptible to dengue infection, and a substantial proportion of persons older than 65 years could acquire secondary infection and are prone to develop severe dengue. © 2018 Wiley Periodicals, Inc.

Locally acquired Dengue--Key West, Florida, 2009-2010.

PubMed

2010-05-21

Dengue is the most common vector-borne viral disease in the world, causing an estimated 50-100 million infections and 25,000 deaths each year. During 1946-1980, no cases of dengue acquired in the continental United States were reported. Since 1980, a few locally acquired U.S. cases have been confirmed along the Texas-Mexico border, temporally associated with large outbreaks in neighboring Mexican cities. On September 1, 2009, a New York physician notified the Monroe County (Florida) Health Department (MCHD) and the Florida Department of Health (FDOH) of a suspected dengue case in a New York state resident whose only recent travel was to Key West, Florida. CDC confirmed the diagnosis, and a press release was issued to notify the public and Key West physicians of the potential risk for locally acquired dengue infections. In the next 2 weeks, two dengue infections in Key West residents without recent travel were reported and confirmed. Subsequently, enhanced and active surveillance identified 24 more Key West cases during 2009. On April 13, 2010, another Key West dengue case was reported to FDOH, bringing the total to 28. This report describes the first three dengue cases reported in 2009, briefly summarizes the 2010 case, highlights preliminary findings from the ongoing investigation, and outlines measures used to mitigate and control the outbreak. Clinicians should include dengue in the differential diagnosis of acute febrile illnesses in patients who live in or have recently traveled to subtropical areas of the United States or to the tropics.

Cost-Effectiveness of Dengue Vaccination Programs in Brazil

PubMed Central

Shim, Eunha

2017-01-01

The first approved dengue vaccine, CYD-TDV, a chimeric, live-attenuated, tetravalent dengue virus vaccine, was recently licensed in 13 countries, including Brazil. In light of recent vaccine approval, we modeled the cost-effectiveness of potential vaccination policies mathematically based on data from recent vaccine efficacy trials that indicated that vaccine efficacy was lower in seronegative individuals than in seropositive individuals. In our analysis, we investigated several vaccination programs, including routine vaccination, with various vaccine coverage levels and those with and without large catch-up campaigns. As it is unclear whether the vaccine protects against infection or just against disease, our model incorporated both direct and indirect effects of vaccination. We found that in the presence of vaccine-induced indirect protection, the cost-effectiveness of dengue vaccination decreased with increasing vaccine coverage levels because the marginal returns of herd immunity decreases with vaccine coverage. All routine dengue vaccination programs that we considered were cost-effective, reducing dengue incidence significantly. Specifically, a routine dengue vaccination of 9-year-olds would be cost-effective when the cost of vaccination per individual is less than $262. Furthermore, the combination of routine vaccination and large catch-up campaigns resulted in a greater reduction of dengue burden (by up to 93%) than routine vaccination alone, making it a cost-effective intervention as long as the cost per course of vaccination is $255 or less. Our results show that dengue vaccination would be cost-effective in Brazil even with a relatively low vaccine efficacy in seronegative individuals. PMID:28500811

Rural-urban comparisons of dengue seroprevalence in Malaysia.

PubMed

Chew, Cheng Hoon; Woon, Yuan Liang; Amin, Faridah; Adnan, Tassha H; Abdul Wahab, Asmah Hani; Ahmad, Zul Edzhar; Bujang, Mohd Adam; Abdul Hamid, Abdul Muneer; Jamal, Rahman; Chen, Wei Seng; Hor, Chee Peng; Yeap, Lena; Hoo, Ling Ping; Goh, Pik Pin; Lim, Teck Onn

2016-08-18

Each year an estimated 390 million dengue infections occur worldwide. In Malaysia, dengue is a growing public health concern but estimate of its disease burden remains uncertain. We compared the urban-rural difference of dengue seroprevalence and determined age-specific dengue seroprevalence in Malaysia. We undertook analysis on 11,821 subjects from six seroprevalence surveys conducted in Malaysia between 2001 and 2013, which composed of five urban and two rural series. Prevalence of dengue increased with age in both urban and rural locations in Malaysia, which exceeded 90 % among those aged 70 years or beyond. The age-specific rates of the 5 urban surveys overlapped without clear separation among them, while prevalence was lower in younger subjects in rural series than in urban series, the trend reversed in older subjects. There were no differences in the seroprevalence by gender, ethnicity or region. Poisson regression model confirmed the prevalence have not changed in urban areas since 2001 but in rural areas, there was a significant positive time trend such that by year 2008, rural prevalence was as high as in urban areas. Dengue seroprevalence has stabilized but persisted at a high level in urban areas since 2001, and is fast stabilizing in rural areas at the same high urban levels by 2008. The cumulative seroprevalence of dengue exceeds 90 % by the age of 70 years, which translates into 16.5 million people or 55 % of the total population in Malaysia, being infected by dengue by 2013.

Assessing the methods needed for improved dengue mapping: a SWOT analysis.

PubMed

Attaway, David Frost; Jacobsen, Kathryn H; Falconer, Allan; Manca, Germana; Waters, Nigel M

2014-01-01

Dengue fever, a mosquito-borne viral infection, is a growing threat to human health in tropical and subtropical areas worldwide. There is a demand from public officials for maps that capture the current distribution of dengue and maps that analyze risk factors to predict the future burden of disease. To identify relevant articles, we searched Google Scholar, PubMed, BioMed Central, and WHOLIS (World Health Organization Library Database) for published articles with a specific set of dengue criteria between January 2002 and July 2013. After evaluating the currently available dengue models, we identified four key barriers to the creation of high-quality dengue maps: (1) data limitations related to the expense of diagnosing and reporting dengue cases in places where health information systems are underdeveloped; (2) issues related to the use of socioeconomic proxies in places with limited dengue incidence data; (3) mosquito ranges which may be changing as a result of climate changes; and (4) the challenges of mapping dengue events at a variety of scales. An ideal dengue map will present endemic and epidemic dengue information from both rural and urban areas. Overcoming the current barriers requires expanded collaboration and data sharing by geographers, epidemiologists, and entomologists. Enhanced mapping techniques would allow for improved visualizations of dengue rates and risks.

Activity of andrographolide against dengue virus.

PubMed

Panraksa, Patcharee; Ramphan, Suwipa; Khongwichit, Sarawut; Smith, Duncan R

2017-03-01

Dengue is the most prevalent arthropod-transmitted viral illness of humans, with an estimated 100 million symptomatic infections occurring each year and more than 2.5 billion people living at risk of infection. There are no approved antiviral agents against dengue virus, and there is only limited introduction of a dengue vaccine in some countries. Andrographolide is derived from Andrographis paniculata, a medicinal plant traditionally used to treat a number of conditions including infections. The antiviral activity of andrographolide against dengue virus (DENV) serotype 2 was evaluated in two cell lines (HepG2 and HeLa) while the activity against DENV 4 was evaluated in one cell line (HepG2). Results showed that andrographolide had significant anti-DENV activity in both cell lines, reducing both the levels of cellular infection and virus output, with 50% effective concentrations (EC 50 ) for DENV 2 of 21.304 μM and 22.739 μM for HepG2 and HeLa respectively. Time of addition studies showed that the activity of andrographolide was confined to a post-infection stage. These results suggest that andrographolide has the potential for further development as an anti-viral agent for dengue virus infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Dengue Virus Genome Uncoating Requires Ubiquitination.

PubMed

Byk, Laura A; Iglesias, Néstor G; De Maio, Federico A; Gebhard, Leopoldo G; Rossi, Mario; Gamarnik, Andrea V

2016-06-28

The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process. Dengue is the most significant arthropod-borne viral infection in humans. Although the number of cases increases every year, there are no approved therapeutics available for the treatment of dengue infection, and many basic aspects of the viral biology remain elusive. After entry, the viral membrane must fuse with the endosomal membrane to deliver the viral genome into the cytoplasm for translation and replication. A great deal of information has been obtained in the last decade

Dengue 4 Vaccine Development

DTIC Science & Technology

1987-09-01

and monkeys. b) Preparation of a production seed from uncloned Dengue 4 (H241) PDK-35 vaccine isolated from viremic serum of a volunteer vaccinee , and...essentially eradicated from the United States and other developed countries, principally as a result of mass vaccination with the trivalent Sabin...CopU~1C FftE 0~AD( ) DENGUE 4 VACCINE DEVELOPMENT Lf 0, to ANNUAL AND FINAL REPORT0 by 0Nyven J. Marchette, Ph.D. September 1, 1987 (For the period 1

A model of immunomodulatory for dengue infection mm

NASA Astrophysics Data System (ADS)

Zulfa, Annisa; Handayani, Dewi; Nuraini, Nuning

2018-03-01

An immunomodulatory model for dengue infection is constructed in this paper. This study focuses on T-cell compartments and B cells that are immune cells involved in the dengue infection process. Dengue virus-infected monocyte cells release interferons to signal T-cells to activate B-cells and produce antibodies. Immunomodulator acts as a treatment control and aims to increase the numbers of antibodies so it is expected to reduce the number of infected monocyte cells by dengue virus. Numerical simulation shows that the greater the rate of f (t) the immune cells will be stimulated to suppress the number of infected cells.

Projections of increased and decreased dengue incidence under climate change.

PubMed

Williams, C R; Mincham, G; Faddy, H; Viennet, E; Ritchie, S A; Harley, D

2016-10-01

Dengue is the world's most prevalent mosquito-borne disease, with more than 200 million people each year becoming infected. We used a mechanistic virus transmission model to determine whether climate warming would change dengue transmission in Australia. Using two climate models each with two carbon emission scenarios, we calculated future dengue epidemic potential for the period 2046-2064. Using the ECHAM5 model, decreased dengue transmission was predicted under the A2 carbon emission scenario, whereas some increases are likely under the B1 scenario. Dengue epidemic potential may decrease under climate warming due to mosquito breeding sites becoming drier and mosquito survivorship declining. These results contradict most previous studies that use correlative models to show increased dengue transmission under climate warming. Dengue epidemiology is determined by a complex interplay between climatic, human host, and pathogen factors. It is therefore naive to assume a simple relationship between climate and incidence, and incorrect to state that climate warming will uniformly increase dengue transmission, although in general the health impacts of climate change will be negative.

Evaluation of dengue virus strains for human challenge studies.

PubMed

Mammen, M P; Lyons, A; Innis, B L; Sun, W; McKinney, D; Chung, R C Y; Eckels, K H; Putnak, R; Kanesa-thasan, N; Scherer, J M; Statler, J; Asher, L V; Thomas, S J; Vaughn, D W

2014-03-14

Discordance between the measured levels of dengue virus neutralizing antibody and clinical outcomes in the first-ever efficacy study of a dengue tetravalent vaccine (Lancet, Nov 2012) suggests a need to re-evaluate the process of pre-screening dengue vaccine candidates to better predict clinical benefit prior to large-scale vaccine trials. In the absence of a reliable animal model and established correlates of protection for dengue, a human dengue virus challenge model may provide an approach to down-select vaccine candidates based on their ability to reduce risk of illness following dengue virus challenge. We report here the challenge of flavivirus-naïve adults with cell culture-passaged dengue viruses (DENV) in a controlled setting that resulted in uncomplicated dengue fever (DF). This sets the stage for proof-of-concept efficacy studies that allow the evaluation of dengue vaccine candidates in healthy adult volunteers using qualified DENV challenge strains well before they reach field efficacy trials involving children. Fifteen flavivirus-naïve adult volunteers received 1 of 7 DENV challenge strains (n=12) or placebo (n=3). Of the twelve volunteers who received challenge strains, five (two DENV-1 45AZ5 and three DENV-3 CH53489 cl24/28 recipients) developed DF, prospectively defined as ≥2 typical symptoms, ≥48h of sustained fever (>100.4°F) and concurrent viremia. Based on our study and historical data, we conclude that the DENV-1 and DENV-3 strains can be advanced as human challenge strains. Both of the DENV-2 strains and one DENV-4 strain failed to meet the protocol case definition of DF. The other two DENV-4 strains require additional testing as the illness approximated but did not satisfy the case definition of DF. Three volunteers exhibited effusions (1 pleural/ascites, 2 pericardial) and 1 volunteer exhibited features of dengue (rash, lymphadenopathy, neutropenia and thrombocytopenia), though in the absence of fever and symptoms. The occurrence of

Dengue Haemorrhagic Encephalitis: Rare Case Report with Review of Literature.

PubMed

Kutiyal, Aditya Singh; Malik, Chetanya; Hyanki, Gitika

2017-07-01

Dengue is an endemic arboviral infection prevalent especially in tropical countries including Southern and Southeast Asia. Central Nervous System (CNS) involvement in dengue infection is uncommon. Haemorrhagic encephalitis is a rare presentation in dengue. This is a case of a 58-year-old male who presented with fever, petechial rash and altered sensorium. Dengue serology IgM was reactive and MRI brain was suggestive of haemorrhagic encephalitis. Patient was managed in Intensive Care Unit (ICU) but eventually succumbed to his illness. We report this fatal outcome of a common viral infection with unusual neurological presentation to propose an association between dengue and neurotropism and the need to look at dengue infection beyond its classical features.

Spatial Variations in Dengue Transmission in Schools in Thailand

PubMed Central

Ratanawong, Pitcha; Kittayapong, Pattamaporn; Olanratmanee, Phanthip; Wilder-Smith, Annelies; Byass, Peter; Tozan, Yesim; Dambach, Peter; Quiñonez, Carlos Alberto Montenegro; Louis, Valérie R.

2016-01-01

Background Dengue is an important neglected tropical disease, with more than half of the world’s population living in dengue endemic areas. Good understanding of dengue transmission sites is a critical factor to implement effective vector control measures. Methods A cohort of 1,811 students from 10 schools in rural, semi-rural and semi-urban Thailand participated in this study. Seroconversion data and location of participants’ residences and schools were recorded to determine spatial patterns of dengue infections. Blood samples were taken to confirm dengue infections in participants at the beginning and the end of school term. Entomological factors included a survey of adult mosquito density using a portable vacuum aspirator during the school term and a follow up survey of breeding sites of Aedes vectors in schools after the school term. Clustering analyses were performed to detect spatial aggregation of dengue infections among participants. Results A total of 57 dengue seroconversions were detected among the 1,655 participants who provided paired blood samples. Of the 57 confirmed dengue infections, 23 (40.0%) occurred in students from 6 (6.8%) of the 88 classrooms in 10 schools. Dengue infections did not show significant clustering by residential location in the study area. During the school term, a total of 66 Aedes aegypti mosquitoes were identified from the 278 mosquitoes caught in 50 classrooms of the 10 schools. In a follow-up survey of breeding sites, 484 out of 2,399 water containers surveyed (20.2%) were identified as active mosquito breeding sites. Discussion and Conclusion Our findings suggest that dengue infections were clustered among schools and among classrooms within schools. The schools studied were found to contain a large number of different types of breeding sites. Aedes vector densities in schools were correlated with dengue infections and breeding sites in those schools. Given that only a small proportion of breeding sites in the schools

Working towards dengue as a vaccine-preventable disease: challenges and opportunities.

PubMed

Shrivastava, Ambuj; Tripathi, Nagesh K; Dash, Paban K; Parida, Manmohan

2017-10-01

Dengue is an emerging viral disease that affects the human population around the globe. Recent advancements in dengue virus research have opened new avenues for the development of vaccines against dengue. The development of a vaccine against dengue is a challenging task because any of the four serotypes of dengue viruses can cause disease. The development of a dengue vaccine aims to provide balanced protection against all the serotypes. Several dengue vaccine candidates are in the developmental stages such as inactivated, live attenuated, recombinant subunit, and plasmid DNA vaccines. Area covered: The authors provide an overview of the progress made in the development of much needed dengue vaccines. The authors include their expert opinion and their perspectives for future developments. Expert opinion: Human trials of a live attenuated tetravalent chimeric vaccine have clearly demonstrated its potential as a dengue vaccine. Other vaccine candidate molecules such as DENVax, a recombinant chimeric vaccine andTetraVax, are at different stages of development at this time. The authors believe that the novel strategies for testing and improving the immune response of vaccine candidates in humans will eventually lead to the development of a successful dengue vaccine in future.

[Dengue fever cases in Czech workers returning from the Maldives].

PubMed

Trojánek, Milan; Tomíčková, Dora; Roháčová, Hana; Kosina, Pavel; Gebouský, Jan; Dvořák, Jan; Chmelik, Vaclav; Batistová, Květoslava; Husa, Petr; Maixner, Jan; Sojková, Naděžda; Zelená, Hana; Marešová, Vilma; Stejskal, František

2013-09-01

The objective of this study is to present epidemiological characteristics and clinical symptoms of dengue fever cases in Czech workers who acquired the infection while working on the island of Fushivelavaru, Maldives. Furthermore, the study compares the sensitivity of novel direct detection assays, i.e. Real-Time Polymerase Chain Reaction (RT-PCR) and detection of Dengue NS1 antigen. The retrospective study evaluated the clinical course of dengue fever cases in Czech workers returning from a job in the Maldives who were diagnosed with dengue virus infection from September 1 to October 31, 2012. The laboratory diagnosis of dengue fever was based on the serological detection of IgM and IgG antibodies, detection of dengue NS1 antigen by enzyme-linked immunosobent assay (ELISA), and detection of dengue virus DNA by RT-PCR. The infection with dengue virus was confirmed in 18 males with a median age of 40 years (IQR 36-47) who returned from a job in the Maldives. Only one patient required admission to the hospital while the others were treated on an outpatient basis. The most frequently observed symptoms were fever (18), headache (9), muscle and joint pain (8 and 7, respectively), and rash (9). Typical laboratory findings were leukocytopenia and thrombocytopenia, a low CRP level, and elevated aminotransferase activity. The clinical course was uncomplicated in all patients. The dengue NS1 antigen detection (positive in all 10 patients with acute dengue fever) showed significantly higher sensitivity than the detection of viral RNA using RT-PCR (positive in 4 patients), p = 0.011. Although the vast majority of dengue fever cases are diagnosed among travellers returning from the tropics, the presented study points out the risks posed by dengue fever to long-term workers in endemic areas. The infection in the serologically naïve hosts is usually uncomplicated; however, infected persons are at significant risk of developing a severe complicated clinical course if challenged

Influenza Illness among Case-Patients Hospitalized for Suspected Dengue, El Salvador, 2012.

PubMed

Chacon, Rafael; Clara, Alexey Wilfrido; Jara, Jorge; Armero, Julio; Lozano, Celina; El Omeiri, Nathalie; Widdowson, Marc-Alain; Azziz-Baumgartner, Eduardo

2015-01-01

We estimate the proportion of patients hospitalized for suspected dengue that tested positive for influenza virus in El Salvador during the 2012 influenza season. We tested specimens from 321 hospitalized patients: 198 patients with SARI and 123 patients with suspected dengue. Among 121 hospitalized suspected dengue (two co-infected excluded) patients, 28% tested positive for dengue and 19% positive for influenza; among 35 with suspected dengue and respiratory symptoms, 14% were positive for dengue and 39% positive for influenza. One percent presented co-infection between influenza and dengue. Clinicians should consider the diagnosis of influenza among patients with suspected dengue during the influenza season.

Analysis of significant factors for dengue fever incidence prediction.

PubMed

Siriyasatien, Padet; Phumee, Atchara; Ongruk, Phatsavee; Jampachaisri, Katechan; Kesorn, Kraisak

2016-04-16

Many popular dengue forecasting techniques have been used by several researchers to extrapolate dengue incidence rates, including the K-H model, support vector machines (SVM), and artificial neural networks (ANN). The time series analysis methodology, particularly ARIMA and SARIMA, has been increasingly applied to the field of epidemiological research for dengue fever, dengue hemorrhagic fever, and other infectious diseases. The main drawback of these methods is that they do not consider other variables that are associated with the dependent variable. Additionally, new factors correlated to the disease are needed to enhance the prediction accuracy of the model when it is applied to areas of similar climates, where weather factors such as temperature, total rainfall, and humidity are not substantially different. Such drawbacks may consequently lower the predictive power for the outbreak. The predictive power of the forecasting model-assessed by Akaike's information criterion (AIC), Bayesian information criterion (BIC), and the mean absolute percentage error (MAPE)-is improved by including the new parameters for dengue outbreak prediction. This study's selected model outperforms all three other competing models with the lowest AIC, the lowest BIC, and a small MAPE value. The exclusive use of climate factors from similar locations decreases a model's prediction power. The multivariate Poisson regression, however, effectively forecasts even when climate variables are slightly different. Female mosquitoes and seasons were strongly correlated with dengue cases. Therefore, the dengue incidence trends provided by this model will assist the optimization of dengue prevention. The present work demonstrates the important roles of female mosquito infection rates from the previous season and climate factors (represented as seasons) in dengue outbreaks. Incorporating these two factors in the model significantly improves the predictive power of dengue hemorrhagic fever forecasting

Evaluation of dengue fever reports during an epidemic, Colombia.

PubMed

Romero-Vega, Liliana; Pacheco, Oscar; de la Hoz-Restrepo, Fernando; Díaz-Quijano, Fredi Alexander

2014-12-01

OBJECTIVE To assess the validity of dengue fever reports and how they relate to the definition of case and severity. METHODS Diagnostic test assessment was conducted using cross-sectional sampling from a universe of 13,873 patients treated during the fifth epidemiological period in health institutions from 11 Colombian departments in 2013. The test under analyses was the reporting to the National Public Health Surveillance System, and the reference standard was the review of histories identified by active institutional search. We reviewed all histories of patients diagnosed with dengue fever, as well as a random sample of patients with febrile syndromes. The specificity and sensitivity of reports were estimated for this purpose, considering the inverse of the probability of being selected for weighting. The concordance between reporting and the findings of the active institutional search was calculated using Kappa statistics. RESULTS We included 4,359 febrile patients, and 31.7% were classified as compatible with dengue fever (17 with severe dengue fever; 461 with dengue fever and warning signs; 904 with dengue fever and no warning signs). The global sensitivity of reports was 13.2% (95%CI 10.9;15.4) and specificity was 98.4% (95%CI 97.9;98.9). Sensitivity varied according to severity: 12.1% (95%CI 9.3;14.8) for patients presenting dengue fever with no warning signs; 14.5% (95%CI 10.6;18.4) for those presenting dengue fever with warning signs, and 40.0% (95%CI 9.6;70.4) for those with severe dengue fever. Concordance between reporting and the findings of the active institutional search resulted in a Kappa of 10.1%. CONCLUSIONS Low concordance was observed between reporting and the review of clinical histories, which was associated with the low reporting of dengue fever compatible cases, especially milder cases.

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

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

2016-10-01

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. 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. 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%). 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. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Is dengue a disease of poverty? A systematic review.

PubMed

Mulligan, Kate; Dixon, Jenna; Sinn, Chi-Ling Joanna; Elliott, Susan J

2015-02-01

Policy prescriptions for combating dengue fever tend to focus on addressing environmental and social conditions of poverty. However, while poverty has long been considered a determinant of dengue, the research evidence for such a relationship is not well established. Results of a systematic review of the research literature designed to identify and assess the current state of the empirical evidence for the dengue-poverty link reveal a mixed story. Of 260 peer-reviewed articles referencing dengue-poverty relationships, only 12 English-language studies empirically assessed these relationships. Our analysis covering various social and economic conditions of poverty showed no clear associations with dengue rates. While nine of the 12 studies demonstrated some positive associations between measures of dengue and poverty (measured inconsistently through income, education, structural housing condition, overcrowding, and socioeconomic status), nine also presented null results and five with negative results. Of the five studies relating to access to water and sanitation, four reported null associations. Income and physical housing conditions were more consistently correlated with dengue outcomes than other poverty indicators. The small size of this sample, and the heterogeneity of measures and scales used to capture conditions of poverty, make it difficult to assess the strength and consistency of associations between various poverty indicators and dengue outcomes. At present, the global body of eligible English-language peer-reviewed literature investigating dengue-poverty relationships is too small to support a definitive relationship. We conclude that more research, particularly using standardized measures of both outcomes and indicators, is needed to support evidence-informed policies and approaches.

Describing dengue epidemics: Insights from simple mechanistic models

NASA Astrophysics Data System (ADS)

Aguiar, Maíra; Stollenwerk, Nico; Kooi, Bob W.

2012-09-01

We present a set of nested models to be applied to dengue fever epidemiology. We perform a qualitative study in order to show how much complexity we really need to add into epidemiological models to be able to describe the fluctuations observed in empirical dengue hemorrhagic fever incidence data offering a promising perspective on inference of parameter values from dengue case notifications.

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

Assessing the methods needed for improved dengue mapping: a SWOT analysis

PubMed Central

Attaway, David Frost; Jacobsen, Kathryn H; Falconer, Allan; Manca, Germana; Waters, Nigel M

2014-01-01

Introduction Dengue fever, a mosquito-borne viral infection, is a growing threat to human health in tropical and subtropical areas worldwide. There is a demand from public officials for maps that capture the current distribution of dengue and maps that analyze risk factors to predict the future burden of disease. Methods To identify relevant articles, we searched Google Scholar, PubMed, BioMed Central, and WHOLIS (World Health Organization Library Database) for published articles with a specific set of dengue criteria between January 2002 and July 2013. Results After evaluating the currently available dengue models, we identified four key barriers to the creation of high-quality dengue maps: (1) data limitations related to the expense of diagnosing and reporting dengue cases in places where health information systems are underdeveloped; (2) issues related to the use of socioeconomic proxies in places with limited dengue incidence data; (3) mosquito ranges which may be changing as a result of climate changes; and (4) the challenges of mapping dengue events at a variety of scales. Conclusion An ideal dengue map will present endemic and epidemic dengue information from both rural and urban areas. Overcoming the current barriers requires expanded collaboration and data sharing by geographers, epidemiologists, and entomologists. Enhanced mapping techniques would allow for improved visualizations of dengue rates and risks. PMID:25328585

Evaluation of a dengue NS1 antigen detection assay sensitivity and specificity for the diagnosis of acute dengue virus infection.

PubMed

Hermann, Laura L; Thaisomboonsuk, Butsaya; Poolpanichupatam, Yongyuth; Jarman, Richard G; Kalayanarooj, Siripen; Nisalak, Ananda; Yoon, In-Kyu; Fernandez, Stefan

2014-10-01

Currently, no dengue NS1 detection kit has regulatory approval for the diagnosis of acute dengue fever. Here we report the sensitivity and specificity of the InBios DEN Detect NS1 ELISA using a panel of well characterized human acute fever serum specimens. The InBios DENV Detect NS1 ELISA was tested using a panel composed of 334 serum specimens collected from acute febrile patients seeking care in a Bangkok hospital in 2010 and 2011. Of these patients, 314 were found to have acute dengue by either RT-PCR and/or anti-dengue IgM/IgG ELISA. Alongside the InBios NS1 ELISA kit, we compared the performance characteristics of the BioRad Platelia NS1 antigen kit. The InBios NS1 ELISA Ag kit had a higher overall sensitivity (86% vs 72.8%) but equal specificity (100%) compared to the BioRad Platelia kit. The serological status of the patient significantly influenced the outcome. In primary infections, the InBios NS1 kit demonstrated a higher sensitivity (98.8%) than in secondary infections (83.5%). We found significant variation in the sensitivity of the InBios NS1 ELISA kit depending on the serotype of the dengue virus and also found decreasing sensitivity the longer after the onset of illness, showing 100% sensitivity early during illness, but dropping below 50% by Day 7. The InBios NS1 ELISA kit demonstrated high accuracy when compared to the initial clinical diagnosis with greater than 85% agreement when patients were clinically diagnosed with dengue illness. Results presented here suggest the accurate detection of circulating dengue NS1 by the InBios DENV Detect NS1 ELISA can provide clinicians with a useful tool for diagnosis of early dengue infections.

Economic and Disease Burden of Dengue in Mexico

PubMed Central

Undurraga, Eduardo A.; Betancourt-Cravioto, Miguel; Ramos-Castañeda, José; Martínez-Vega, Ruth; Méndez-Galván, Jorge; Gubler, Duane J.; Guzmán, María G.; Halstead, Scott B.; Harris, Eva; Kuri-Morales, Pablo; Tapia-Conyer, Roberto; Shepard, Donald S.

2015-01-01

Background Dengue imposes a substantial economic and disease burden in most tropical and subtropical countries. Dengue incidence and severity have dramatically increased in Mexico during the past decades. Having objective and comparable estimates of the economic burden of dengue is essential to inform health policy, increase disease awareness, and assess the impact of dengue prevention and control technologies. Methods and Findings We estimated the annual economic and disease burden of dengue in Mexico for the years 2010–2011. We merged multiple data sources, including a prospective cohort study; patient interviews and macro-costing from major hospitals; surveillance, budget, and health data from the Ministry of Health; WHO cost estimates; and available literature. We conducted a probabilistic sensitivity analysis using Monte Carlo simulations to derive 95% certainty levels (CL) for our estimates. Results suggest that Mexico had about 139,000 (95%CL: 128,000–253,000) symptomatic and 119 (95%CL: 75–171) fatal dengue episodes annually on average (2010–2011), compared to an average of 30,941 symptomatic and 59 fatal dengue episodes reported. The annual cost, including surveillance and vector control, was US$170 (95%CL: 151–292) million, or $1.56 (95%CL: 1.38–2.68) per capita, comparable to other countries in the region. Of this, $87 (95%CL: 87–209) million or $0.80 per capita (95%CL: 0.62–1.12) corresponds to illness. Annual disease burden averaged 65 (95%CL: 36–99) disability-adjusted life years (DALYs) per million population. Inclusion of long-term sequelae, co-morbidities, impact on tourism, and health system disruption during outbreaks would further increase estimated economic and disease burden. Conclusion With this study, Mexico joins Panama, Puerto Rico, Nicaragua, and Thailand as the only countries or areas worldwide with comprehensive (illness and preventive) empirical estimates of dengue burden. Burden varies annually; during an outbreak

The history of dengue outbreaks in the Americas.

PubMed

Brathwaite Dick, Olivia; San Martín, José L; Montoya, Romeo H; del Diego, Jorge; Zambrano, Betzana; Dayan, Gustavo H

2012-10-01

Dengue is a viral disease usually transmitted by Aedes aegypti mosquitoes. Dengue outbreaks in the Americas reported in medical literature and to the Pan American Health Organization are described. The outbreak history from 1600 to 2010 was categorized into four phases: Introduction of dengue in the Americas (1600-1946); Continental plan for the eradication of the Ae. aegypti (1947-1970) marked by a successful eradication of the mosquito in 18 continental countries by 1962; Ae. aegypti reinfestation (1971-1999) caused by the failure of the mosquito eradication program; Increased dispersion of Ae. aegypti and dengue virus circulation (2000-2010) characterized by a marked increase in the number of outbreaks. During 2010 > 1.7 million dengue cases were reported, with 50,235 severe cases and 1,185 deaths. A dramatic increase in the number of outbreaks has been reported in recent years. Urgent global action is needed to avoid further disease spread.

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

Dengue Virus 1 Outbreak in Buenos Aires, Argentina, 2016.

PubMed

Tittarelli, Estefanía; Lusso, Silvina B; Goya, Stephanie; Rojo, Gabriel L; Natale, Mónica I; Viegas, Mariana; Mistchenko, Alicia S; Valinotto, Laura E

2017-10-01

The largest outbreak of dengue in Buenos Aires, Argentina, occurred during 2016. Phylogenetic, phylodynamic, and phylogeographic analyses of 82 samples from dengue patients revealed co-circulation of 2 genotype V dengue virus lineages, suggesting that this virus has become endemic to the Buenos Aires metropolitan area.

Transmission Dinamics Model Of Dengue Fever

NASA Astrophysics Data System (ADS)

Debora; Rendy; Rahmi

2018-01-01

Dengue fever is an endemic disease that is transmitted through the Aedes aegypti mosquito vector. The disease is present in more than 100 countries in America, Africa, and Asia, especially tropical countries. Differential equations can be used to represent the spread of dengue virus occurring in time intervals and model in the form of mathematical models. The mathematical model in this study tries to represent the spread of dengue fever based on the data obtained and the assumptions used. The mathematical model used is a mathematical model consisting of Susceptible (S), Infected (I), Viruses (V) subpopulations. The SIV mathematical model is then analyzed to see the solution behaviour of the system.

Autoimmune features caused by dengue fever: a case report.

PubMed

Jardim, Denis Leonardo Fontes; Tsukumo, Daniela Miti Lemos; Angerami, Rodrigo N; Carvalho Filho, Marco Antonio de; Saad, Mário José Abdalla

2012-01-01

Dengue virus is the most important mosquito-borne viral disease in the world. Co-circulation of the four types of dengue viruses and expansion of dengue epidemic gave rise to infection enhancement and a big expansion of clinical aspects of the disease. Herein we report a case of a 25-year-old white woman with dengue fever and numerous associated autoimmune features. Our patient had proteinuria, an extensive right pleural effusion, a thin pericardial effusion and ascites. She had a low C3 level and positive antinuclear antibody; cryoglobulins were also positive. The numerous autoimmune features of this patient were a diagnostic challenge, since she was a young woman and could be easily mistaken for a rheumatologic patient in a newly open disease. Dengue infection probably was a triggering event causing an abnormal immune response. Therefore, dengue should be suspected in patients with hematological disorders and autoimmune features in endemic regions or those who have travelled to those regions.

Economic Cost and Burden of Dengue in the Philippines

PubMed Central

Edillo, Frances E.; Halasa, Yara A.; Largo, Francisco M.; Erasmo, Jonathan Neil V.; Amoin, Naomi B.; Alera, Maria Theresa P.; Yoon, In-Kyu; Alcantara, Arturo C.; Shepard, Donald S.

2015-01-01

Dengue, the world's most important mosquito-borne viral disease, is endemic in the Philippines. During 2008–2012, the country's Department of Health reported an annual average of 117,065 dengue cases, placing the country fourth in dengue burden in southeast Asia. This study estimates the country's annual number of dengue episodes and their economic cost. Our comparison of cases between active and passive surveillance in Punta Princesa, Cebu City yielded an expansion factor of 7.2, close to the predicted value (7.0) based on the country's health system. We estimated an annual average of 842,867 clinically diagnosed dengue cases, with direct medical costs (in 2012 US dollars) of $345 million ($3.26 per capita). This is 54% higher than an earlier estimate without Philippines-specific costs. Ambulatory settings treated 35% of cases (representing 10% of direct costs), whereas inpatient hospitals served 65% of cases (representing 90% of direct costs). The economic burden of dengue in the Philippines is substantial. PMID:25510723

Underrecognition of Dengue during 2013 Epidemic in Luanda, Angola

PubMed Central

Moreira, Rosa; Soares, Maria José; Miguel da Costa, Lúis; Mann, Jennifer; DeLorey, Mark; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L.; Colón, Candimar; Margolis, Harold S.; de Caravalho, Adelaide; Tomashek, Kay M.

2015-01-01

During the 2013 dengue epidemic in Luanda, Angola, 811 dengue rapid diagnostic test–positive cases were reported to the Ministry of Health. To better understand the magnitude of the epidemic and identify risk factors for dengue virus (DENV) infection, we conducted cluster surveys around households of case-patients and randomly selected households 6 weeks after the peak of the epidemic. Of 173 case cluster participants, 16 (9%) exhibited evidence of recent DENV infection. Of 247 random cluster participants, 25 (10%) had evidence of recent DENV infection. Of 13 recently infected participants who had a recent febrile illness, 7 (54%) had sought medical care, and 1 (14%) was hospitalized with symptoms consistent with severe dengue; however, none received a diagnosis of dengue. Behavior associated with protection from DENV infection included recent use of mosquito repellent or a bed net. These findings suggest that the 2013 dengue epidemic was larger than indicated by passive surveillance data. PMID:26196224

Dengue Hemorrhagic Fever Virus in Saudi Arabia: A Review.

PubMed

Al-Tawfiq, Jaffar A; Memish, Ziad A

2018-02-01

Dengue fever is a global disease with a spectrum of clinical manifestation ranging from mild febrile disease to a severe disease in the form of dengue hemorrhagic fever and dengue shock syndrome. Dengue virus is one viral hemorrhagic fever that exists in the Kingdom of Saudi Arabia in addition to Alkhurma (Alkhurma) Hemorrhagic Fever, Chikungunya virus, Crimean-Congo Hemorrhagic Fever, and Rift Valley Fever. The disease is limited to the Western and South-western regions of Saudi Arabia, where Aedes aegypti exists. The majority of the cases in Saudi Arabia had mild disease and is related to serotypes 1-3 but not 4. The prospect for Dengue virus control relies on vector control, health education, and possibly vaccine use. Despite extensive collaborative efforts between multiple governmental sectors, including Ministry of Health, Ministry of Municipalities and Rural Affairs, and Ministry of Water, dengue remains a major public health concern in the regions affected.

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

Vaccines licensed and in clinical trials for the prevention of dengue.

PubMed

Torresi, J; Ebert, G; Pellegrini, M

2017-05-04

Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1-80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans.

Vaccines licensed and in clinical trials for the prevention of dengue

PubMed Central

Torresi, J.; Ebert, G.; Pellegrini, M.

2017-01-01

ABSTRACT Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1–80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans. PMID:28281864

[Dengue, Zika and Chikungunya].

PubMed

Kantor, Isabel N

2016-01-01

Arboviruses are transmitted by arthropods, including those responsible for the current pandemic: alphavirus (Chikungunya) and flaviviruses (dengue and Zika). Its importance increased in the Americas over the past 20 years. The main vectors are Aedes aegypti and A. albopictus. Dengue infection provides long lasting immunity against the specific serotype and temporary to the other three. Subsequent infection by another serotype determines more serious disease. There is a registered vaccine for dengue, Dengvaxia (Sanofi Pasteur). Other two (Butantan and Takeda) are in Phase III in 2016. Zika infection is usually asymptomatic or occurs with rash, conjunctivitis and not very high fever. There is no vaccine or specific treatment. It can be transmitted by parental, sexual and via blood transfusion. It has been associated with microcephaly. Chikungunya causes prolonged joint pain and persistent immune response. Two candidate vaccines are in Phase II. Dengue direct diagnosis is performed by virus isolation, RT-PCR and ELISA for NS1 antigen detection; indirect methods are ELISA-IgM (cross-reacting with other flavivirus), MAC-ELISA, and plaque neutralization. Zika is diagnosed by RT-PCR and virus isolation. Serological diagnosis cross-reacts with other flavivirus. For CHIKV culture, RT-PCR, MAC-ELISA and plaque neutralization are used. Against Aedes organophosphate larvicides (temephos), organophosphorus insecticides (malathion and fenitrothion) and pyrethroids (permethrin and deltamethrin) are usually employed. Resistance has been described to all these products. Vegetable derivatives are less expensive and biodegradable, including citronella oil, which microencapsulated can be preserved from evaporation.

Determination of clusters and factors associated with dengue dispersion during the first epidemic related to Dengue virus serotype 4 in Vitória, Brazil

PubMed Central

Herbinger, Karl-Heinz; Cerutti Junior, Crispim; Malta Romano, Camila; de Souza Areias Cabidelle, Aline; Fröschl, Günter

2017-01-01

Dengue occurrence is partially influenced by the immune status of the population. Consequently, the introduction of a new Dengue virus serotype can trigger explosive epidemics in susceptible populations. The determination of clusters in this scenario can help to identify hotspots and understand the disease dispersion regardless of the influence of the population herd immunity. The present study evaluated the pattern and factors associated with dengue dispersion during the first epidemic related to Dengue virus serotype 4 in Vitória, Espírito Santo state, Brazil. Data on 18,861 dengue cases reported in Vitória from September 2012 to June 2013 were included in the study. The analysis of spatial variation in temporal trend was performed to detect clusters that were compared by their respective relative risk, house index, population density, and income in an ecological study. Overall, 11 clusters were detected. The time trend increase of dengue incidence in the overall study population was 636%. The five clusters that showed a lower time trend increase than the overall population presented a higher incidence in the beginning of the epidemic and, compared to the six clusters with higher time trend increase, they presented higher relative risk for their inhabitants to acquire dengue infection (P-value = 0.02) and a lower income (P-value <0.01). House index and population density did not differ between the clusters. Early increase of dengue incidence and higher relative risk for acquiring dengue infection were favored in low-income areas. Preventive actions and improvement of infrastructure in low-income areas should be prioritized in order to diminish the magnitude of dengue dispersion after the introduction of a new serotype. PMID:28388694

Dengue fever in the San Juan Bay Estuary: Evaluating the ...

EPA Pesticide Factsheets

Dengue is transmitted by Aedes aegypti, a species that thrives in cities. Here we ask which elements within the urban environment could be managed to reduce the potential for Dengue occurrence. In particular, we study the potential of wetlands in the SJBE to buffer from vector proliferation. Wetlands provide ecosystem services such as heat and water hazard mitigation, water purification and habitat for a diversity of species, all of which are factors that have been shown to affect Dengue vectors. As such, we hypothesize that within coastal neighborhoods in the SJBE wetlands, ecosystem services lead to lower Dengue occurrence. We test this hypothesis using Dengue data from 2010-2013, which includes the largest epidemic in PR history. Our analytical model includes relevant socio-economic factors and environmental controls that may also affect Dengue dynamics. Results indicated a negative effect of neighborhood mangrove cover and a positive effect of percent flood area on Dengue prevalence. Moreover, heat hazards were positively correlated with dengue prevalence and negatively correlated with neighborhood mangrove cover. Dengue prevalence did not correlate with herbaceous wetlands, or with the ecosystem services of water quality or vertebrate species richness. Mosquito borne diseases are an increasingly important health concern, which pose great challenges for safe and sustainable control and eradication. This reality calls for management approaches that consider m

Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

DTIC Science & Technology

1982-07-01

r AD Af29 019 PA I4OGENESIS OF DENGUE VACCINE VIRUSES IN MOSQITOES U) YALE UNIV NEW YIAVEN CONN SCHOOL OF MEDICINE B JBEAT ET AL 01 JUL 82 DAMD1779...1963-A ’UNCLASS IFIET) .AD.- PATHOGENESIS OF DENGUE VACCINE VIRUSES IN MOSQUITOES FINAL REPORT Barry J. Beaty, Ph.D. Thomas H. G. Aitken, Ph.D. July 1...NUMBER 4. TITLE (mid Subdl.) S. KVPE OF REPORT & PERIOD COVERED PATHOGENESIS OF DENGUE VACCINE VIRUSES Final Scientific Report IN MOSQUITOES 6/1/79 to 6

Risk factors for concurrent bacteremia in adult patients with dengue.

PubMed

Thein, Tun-Linn; Ng, Ee-Ling; Yeang, Ming S; Leo, Yee-Sin; Lye, David C

2017-06-01

Bacteremia in dengue may occur with common exposure to pathogens in association with severe organ impairment or severe dengue, which may result in death. Cohort studies identifying risk factors for concurrent bacteremia among patients with dengue are rare. We conducted a retrospective case-control study of adult patients with dengue who were admitted to the Department of Infectious Diseases at Tan Tock Seng Hospital, Singapore from 2004 to 2008. For each case of dengue with concurrent bacteremia (within the first 72 hours of admission), we selected four controls without bacteremia, who were matched on year of infection and dengue confirmation method. Conditional logistic regression was performed to identify risk factors for concurrent bacteremia. Among 9,553 patients with dengue, 29 (0.3%) had bacteremia. Eighteen of these patients (62.1%) had concurrent bacteremia. The predominant bacteria were Staphylococcus aureus, one of which was a methicillin-resistant strain. Dengue shock syndrome occurred more frequently and hospital stay was longer among cases than among controls. Three cases did not survive, whereas none of the controls died. In multivariate analysis, being critically ill at hospital presentation was independently associated with 15 times the likelihood of a patient with dengue having concurrent bacteremia. Concurrent bacteremia in adult patients with dengue is uncommon but presents atypically and results in more deaths and longer hospital stay. Given the associated mortality, collection of blood cultures and empiric antibiotic therapy may be considered in patients who are critically ill. Copyright © 2015. Published by Elsevier B.V.

[Coexistence of acute appendicitis and dengue fever: A case report].

PubMed

Osuna-Ramos, Juan Fidel; Silva-Gracia, Carlos; Maya-Vacio, Gerardo Joel; Romero-Utrilla, Alejandra; Ríos-Burgueño, Efrén Rafael; Velarde-Félix, Jesús Salvador

2017-12-01

Dengue is the most important human viral disease transmitted by mosquitoes. It can be asymptomatic or it can present in any of its 3clinical forms: Dengue fever, dengue haemorrhagic fever and dengue shock syndrome. However, some atypical manifestations have been reported in surgical emergencies caused by acute appendicitis in patients with dengue fever. We report the case of an 18-year-old Mexican male who presented to the emergency department of the General Hospital of Culiacan, Sinaloa, with symptoms of dengue fever, accompanied by crampy abdominal pain with positive Rovsing and Dunphy signs. Dengue infection was confirmed by a positive NS1 antigen test performed by enzyme-linked immunosorbent assay. An abdominal ultrasound revealed an appendicular process; as the abdominal pain in the right side kept increasing, an open appendectomy was performed. Abundant inflammatory liquid was observed during the surgery, and the pathology laboratory reported an oedematous appendix with fibrinopurulent plaques, which agreed with acute ulcerative appendicitis. The patient was discharged fully recovered without complications during the follow-up period. Acute abdominal pain can be caused in some cases by dengue infection. This can be confusing, which can lead to unnecessary surgical interventions, creating additional morbidities and costs for the patient. This unusual and coincident acute appendicitis with dengue highlights the importance of performing careful clinical studies for appropriate decision making, especially in dengue endemic regions during an outbreak of this disease. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Increased Levels of Txa₂ Induced by Dengue Virus Infection in IgM Positive Individuals Is Related to the Mild Symptoms of Dengue.

PubMed

Oliveira, Eneida S; Colombarolli, Stella G; Nascimento, Camila S; Batista, Izabella C A; Ferreira, Jorge G G; Alvarenga, Daniele L R; de Sousa, Laís O B; Assis, Rafael R; Rocha, Marcele N; Alves, Érica A R; Calzavara-Silva, Carlos E

2018-02-28

The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus -induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated. Dengue virus infection increases the levels of thromboxane A2 in IgM-positive individuals as well as the amount of lipid bodies in monocytes in IgM-negative individuals. We suggest that increased levels of thromboxane A2 in IgM-positive individuals plays a protective role against the development of severe symptoms of dengue, such as vascular leakage.

"Preliminary Seroepidemiological survey of dengue infections in Pakistan, 2009-2014".

PubMed

Suleman, Muhammad; Lee, Hyeong-Woo; Zaidi, Syed Sohail Zahoor; Alam, Muhammad Masroor; Nisar, Nadia; Aamir, Uzma Bashir; Sharif, Salmaan; Shaukat, Shahzad; Khurshid, Adnan; Angez, Mehar; Umair, Massab; Mujtaba, Ghulam; Faryal, Rani

2017-03-09

Dengue virus is the causative agent of dengue fever, a vector borne infection which causes self-limiting to life threatening disease in humans. A sero-epidemiological study was conducted to understand the current epidemiology of dengue virus in Pakistan which is now known as a dengue endemic country after its first reported outbreak in 1994. To investigate the prevalence of dengue virus in Pakistan during 2009-2014, a total of 9,493 blood samples were screened for the detection of anti-dengue IgM antibodies using ELISA. Clinical and demographic features available with hospital records were reviewed to ascertain mortalities related to dengue hemorrhagic shock syndrome. Out of 9,493 samples tested, 37% (3,504) were found positive for anti-dengue IgM antibodies. Of the seropositive cases, 73.6% (2,578/3,504) were male and 26.4% (926/3,504) were female. The highest number (382/929; 41.1%) of sero-positive cases was observed among the individuals of age group 31-40 years. The highest number of symptomatic cases was reported in October (46%; 4,400/9,493), and the highest number of sero-positive cases among symptomatic cases was observed in November (45.7%; 806/1,764). Mean annual patient incidence (MAPI) during 2009-2014 in Pakistan remained 0.30 with the highest annual patient incidence (11.03) found in Islamabad. According to the available medical case record, 472 dengue related deaths were reported during 2009-2014. The data from earlier reports in Pakistan described the dengue virus incidence from limited areas of the country. Our findings are important considering the testing of clinical samples at a larger scale covering patients of vast geographical regions and warrants timely implementation of dengue vector surveillance and control programs. It is an epidemiological research study, so trial registration is not required.

Licensed Dengue Vaccine: Public Health Conundrum and Scientific Challenge.

PubMed

Halstead, Scott B

2016-10-05

A tetravalent live attenuated vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (chimeric yellow fever dengue [CYD]) manufactured by Sanofi Pasteur has completed phase III clinical testing in over 35,000 children 2-16 years of age. The vaccine was recently licensed in four countries. During the first 2 years of observation, CYD vaccine efficacy ranged between 30% and 79% in 10 different countries with an overall efficacy of 56.8%. During year 3, there was an overall efficacy against hospitalization of 16.7%, but a relative risk of hospitalization of 1.6 among children younger than 9 years and 4.95 in children 5 years of age and younger. Vaccination of seronegative children resulted in universal broad dengue neutralizing antibody responses, but poor protection against breakthrough dengue cases. Unless proven otherwise, such breakthrough cases in vaccinated subjects should be regarded as vaccine antibody-enhanced (ADE). The provenance of these cases can be studied serologically using original antigenic sin immune responses in convalescent sera. In conventional dengue vaccine efficacy clinical trials, persons vaccinated as seronegatives may be hospitalized with breakthrough ADE infections, whereas in the placebo group, dengue infection of monotypic immunes results in hospitalization. Vaccine efficacy trial design must identify dengue disease etiology by separately measuring efficacy in seronegatives and seropositives. The reason(s) why CYD vaccine failed to raise protective dengue virus immunity are unknown. To achieve a safe and protective dengue vaccine, careful studies of monotypic CYD vaccines in humans should precede field trials of tetravalent formulations. © The American Society of Tropical Medicine and Hygiene.

Meteorologically Driven Simulations of Dengue Epidemics in San Juan, PR

PubMed Central

Morin, Cory W.; Monaghan, Andrew J.; Hayden, Mary H.; Barrera, Roberto; Ernst, Kacey

2015-01-01

Meteorological factors influence dengue virus ecology by modulating vector mosquito population dynamics, viral replication, and transmission. Dynamic modeling techniques can be used to examine how interactions among meteorological variables, vectors and the dengue virus influence transmission. We developed a dengue fever simulation model by coupling a dynamic simulation model for Aedes aegypti, the primary mosquito vector for dengue, with a basic epidemiological Susceptible-Exposed-Infectious-Recovered (SEIR) model. Employing a Monte Carlo approach, we simulated dengue transmission during the period of 2010–2013 in San Juan, PR, where dengue fever is endemic. The results of 9600 simulations using varied model parameters were evaluated by statistical comparison (r2) with surveillance data of dengue cases reported to the Centers for Disease Control and Prevention. To identify the most influential parameters associated with dengue virus transmission for each period the top 1% of best-fit model simulations were retained and compared. Using the top simulations, dengue cases were simulated well for 2010 (r2 = 0.90, p = 0.03), 2011 (r2 = 0.83, p = 0.05), and 2012 (r2 = 0.94, p = 0.01); however, simulations were weaker for 2013 (r2 = 0.25, p = 0.25) and the entire four-year period (r2 = 0.44, p = 0.002). Analysis of parameter values from retained simulations revealed that rain dependent container habitats were more prevalent in best-fitting simulations during the wetter 2010 and 2011 years, while human managed (i.e. manually filled) container habitats were more prevalent in best-fitting simulations during the drier 2012 and 2013 years. The simulations further indicate that rainfall strongly modulates the timing of dengue (e.g., epidemics occurred earlier during rainy years) while temperature modulates the annual number of dengue fever cases. Our results suggest that meteorological factors have a time-variable influence on dengue transmission relative to other important

Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions.

PubMed

Martelli, Celina Maria Turchi; Siqueira, Joao Bosco; Parente, Mirian Perpetua Palha Dias; Zara, Ana Laura de Sene Amancio; Oliveira, Consuelo Silva; Braga, Cynthia; Pimenta, Fabiano Geraldo; Cortes, Fanny; Lopez, Juan Guillermo; Bahia, Luciana Ribeiro; Mendes, Marcia Costa Ooteman; da Rosa, Michelle Quarti Machado; de Siqueira Filha, Noemia Teixeira; Constenla, Dagna; de Souza, Wayner Vieira

2015-01-01

Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil. We estimated the economic burden of dengue in Brazil for the years 2009 to 2013 and for the epidemic season of August 2012- September 2013. We conducted a multicenter cohort study across four endemic regions: Midwest, Goiania; Southeast, Belo Horizonte and Rio de Janeiro; Northeast: Teresina and Recife; and the North, Belem. Ambulatory or hospitalized cases with suspected or laboratory-confirmed dengue treated in both the private and public sectors were recruited. Interviews were scheduled for the convalescent period to ascertain characteristics of the dengue episode, date of first symptoms/signs and recovery, use of medical services, work/school absence, household spending (out-of-pocket expense) and income lost using a questionnaire developed for a previous cost study. We also extracted data from the patients' medical records for hospitalized cases. Overall costs per case and cumulative costs were calculated from the public payer and societal perspectives. National cost estimations took into account cases reported in the official notification system (SINAN) with adjustment for underreporting of cases. We applied a probabilistic sensitivity analysis using Monte Carlo simulations with 90% certainty levels (CL). We screened 2,223 cases, of which 2,035 (91.5%) symptomatic dengue cases were included in our study. The estimated cost for dengue for the epidemic season (2012-2013) in the societal perspective was US$ 468 million (90% CL: 349-590) or US$ 1,212 million (90% CL: 904-1,526) after adjusting for under-reporting. Considering the time series of dengue (2009-2013) the estimated cost of dengue varied from US$ 371 million (2009) to US$ 1,228 million (2013). The economic burden associated with dengue in Brazil is substantial with

Dengue Surveillance in Veterans Affairs Healthcare Facilities, 2007–2010

PubMed Central

Schirmer, Patricia L.; Lucero-Obusan, Cynthia A.; Benoit, Stephen R.; Santiago, Luis M.; Stanek, Danielle; Dey, Achintya; Martinez, Mirsonia; Oda, Gina; Holodniy, Mark

2013-01-01

Background Although dengue is endemic in Puerto Rico (PR), 2007 and 2010 were recognized as epidemic years. In the continental United States (US), outside of the Texas-Mexico border, there had not been a dengue outbreak since 1946 until dengue re-emerged in Key West, Florida (FL), in 2009–2010. The objective of this study was to use electronic and manual surveillance systems to identify dengue cases in Veterans Affairs (VA) healthcare facilities and then to clinically compare dengue cases in Veterans presenting for care in PR and in FL. Methodology Outpatient encounters from 1/2007–12/2010 and inpatient admissions (only available from 10/2009–12/2010) with dengue diagnostic codes at all VA facilities were identified using VA's Electronic Surveillance System for Early Notification of Community-based Epidemics (ESSENCE). Additional case sources included VA data from Centers for Disease Control and Prevention BioSense and VA infection preventionists. Case reviews were performed. Categorical data was compared using Mantel-Haenszel or Fisher Exact tests and continuous variables using t-tests. Dengue case residence was mapped. Findings Two hundred eighty-eight and 21 PR and FL dengue cases respectively were identified. Of 21 FL cases, 12 were exposed in Key West and 9 were imported. During epidemic years, FL cases had significantly increased dengue testing and intensive care admissions, but lower hospitalization rates and headache or eye pain symptoms compared to PR cases. There were no significant differences in clinical symptoms, laboratory abnormalities or outcomes between epidemic and non-epidemic year cases in FL and PR. Confirmed/probable cases were significantly more likely to be hospitalized and have thrombocytopenia or leukopenia compared to suspected cases. Conclusions Dengue re-introduction in the continental US warrants increased dengue surveillance and education in VA. Throughout VA, under-testing of suspected cases highlights the need to emphasize use

Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions

PubMed Central

Martelli, Celina Maria Turchi; Siqueira, Joao Bosco; Parente, Mirian Perpetua Palha Dias; Zara, Ana Laura de Sene Amancio; Oliveira, Consuelo Silva; Braga, Cynthia; Pimenta, Fabiano Geraldo; Cortes, Fanny; Lopez, Juan Guillermo; Bahia, Luciana Ribeiro; Mendes, Marcia Costa Ooteman; da Rosa, Michelle Quarti Machado; de Siqueira Filha, Noemia Teixeira; Constenla, Dagna; de Souza, Wayner Vieira

2015-01-01

Background Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil. Methods We estimated the economic burden of dengue in Brazil for the years 2009 to 2013 and for the epidemic season of August 2012- September 2013. We conducted a multicenter cohort study across four endemic regions: Midwest, Goiania; Southeast, Belo Horizonte and Rio de Janeiro; Northeast: Teresina and Recife; and the North, Belem. Ambulatory or hospitalized cases with suspected or laboratory-confirmed dengue treated in both the private and public sectors were recruited. Interviews were scheduled for the convalescent period to ascertain characteristics of the dengue episode, date of first symptoms/signs and recovery, use of medical services, work/school absence, household spending (out-of-pocket expense) and income lost using a questionnaire developed for a previous cost study. We also extracted data from the patients’ medical records for hospitalized cases. Overall costs per case and cumulative costs were calculated from the public payer and societal perspectives. National cost estimations took into account cases reported in the official notification system (SINAN) with adjustment for underreporting of cases. We applied a probabilistic sensitivity analysis using Monte Carlo simulations with 90% certainty levels (CL). Results We screened 2,223 cases, of which 2,035 (91.5%) symptomatic dengue cases were included in our study. The estimated cost for dengue for the epidemic season (2012–2013) in the societal perspective was US$ 468 million (90% CL: 349–590) or US$ 1,212 million (90% CL: 904–1,526) after adjusting for under-reporting. Considering the time series of dengue (2009–2013) the estimated cost of dengue varied from US$ 371 million (2009) to US$ 1,228 million (2013). Conclusions The economic burden

Quantifying the Emergence of Dengue in Hanoi, Vietnam: 1998–2009

PubMed Central

Cuong, Hoang Quoc; Hien, Nguyen Tran; Duong, Tran Nhu; Phong, Tran Vu; Cam, Nguyen Nhat; Farrar, Jeremy; Nam, Vu Sinh; Thai, Khoa T. D.; Horby, Peter

2011-01-01

Background An estimated 2.4 billion people live in areas at risk of dengue transmission, therefore the factors determining the establishment of endemic dengue in areas where transmission suitability is marginal is of considerable importance. Hanoi, Vietnam is such an area, and following a large dengue outbreak in 2009, we set out to determine if dengue is emerging in Hanoi. Methods and Principal Findings We undertook a temporal and spatial analysis of 25,983 dengue cases notified in Hanoi between 1998 and 2009. Age standardized incidence rates, standardized age of infection, and Standardized Morbidity Ratios (SMR) were calculated. A quasi-Poisson regression model was used to determine if dengue incidence was increasing over time. Wavelet analysis was used to explore the periodicity of dengue transmission and the association with climate variables. After excluding the two major outbreak years of 1998 and 2009 and correcting for changes in population age structure, we identified a significant annual increase in the incidence of dengue cases over the period 1999–2008 (incidence rate ratio  = 1.38, 95% confidence interval  = 1.20–1.58, p value  = 0.002). The age of notified dengue cases in Hanoi is high, with a median age of 23 years (mean 26.3 years). After adjusting for changes in population age structure, there was no statistically significant change in the median or mean age of dengue cases over the period studied. Districts in the central, highly urban, area of Hanoi have the highest incidence of dengue (SMR>3). Conclusions Hanoi is a low dengue transmission setting where dengue incidence has been increasing year on year since 1999. This trend needs to be confirmed with serological surveys, followed by studies to determine the underlying drivers of this emergence. Such studies can provide insights into the biological, demographic, and environmental changes associated with vulnerability to the establishment of endemic dengue. PMID:21980544

Dengue fever presenting with acute cerebellitis: a case report.

PubMed

Withana, Milinda; Rodrigo, Chaturaka; Chang, Thashi; Karunanayake, Panduka; Rajapakse, Senaka

2014-03-05

The incidence of dengue fever is on the rise in tropical countries. In Sri Lanka, nearly 45,000 patients were reported in 2012. With the increasing numbers, rare manifestations of dengue are occasionally encountered. We report a patient who presented with bilateral cerebellar signs as the presenting feature of dengue. A 45-year-old previously healthy female from the suburbs of Colombo, Sri Lanka presented with an acute febrile illness associated with unsteadiness of gait. Clinical examination revealed a scanning dysarthria and marked horizontal nystagmus with bilateral dysmetria, dysdiadokokinesia and incordination more prominent on the right. Her gait was wide-based and ataxic with a tendency to fall to the right more than to the left. Dengue nonstructural protein antigen 1 test and IgM antibody testing both became positive indicating acute dengue infection. She recovered from the febrile episode within 9 days since the onset of fever but cerebellar symptoms outlasted the fever by one week. The magnetic resonance imaging of brain was normal and cerebellar signs resolved spontaneously by day 17 of the illness. Cerebellar syndrome in association with dengue fever has been reported in only four instances and our patient is the first reported case of dengue fever presenting with cerebellitis as the first manifestation of disease. This case report is intended to highlight the occurrence of acute cerebellitis as a presenting syndrome of the expanding list of unusual neurological manifestations of dengue infection.

Dengue vaccines: Are they safe for travelers?

PubMed

Halstead, Scott B; Aguiar, Maira

2016-01-01

The four dengue viruses (DENV) circulate among nearly one-half of the world's population in tropical and semitropical countries imposing a huge morbidity burden on travelers. Sanofipasteur has developed a tetravalent live-attenuated vaccine, Dengvaxia, recently approved by the World Health Organization and licensed in four dengue-endemic countries. An additional two dengue vaccines, developed by the National Institute of Allergy and Infectious Diseases (NIAID), USA and Takeda, are entering phase III testing. Dengvaxia is composed of four yellow fever 17D-DENV chimeras, the NIAID vaccine contains three mutagenized DENV and one DENV2/4 chimera while the Takeda vaccine contains an attenuated DENV 2 and three DENV 2-DENV chimeras. Which of these vaccines might be useful in protecting travelers against dengue infections and disease? Dengvaxia requires three doses administered over the course of one year but in addition has safety signals suggesting that susceptible individuals should not be vaccinated. The NIAID vaccine is promising as a travel vaccine as a single dose fully protected susceptible adults against live dengue 2 virus challenge. The protective efficacy and safety of the Takeda vaccine remain to be demonstrated. Copyright © 2016 Elsevier Ltd. All rights reserved.

The History of Dengue Outbreaks in the Americas

PubMed Central

Brathwaite Dick, Olivia; San Martín, José L.; Montoya, Romeo H.; del Diego, Jorge; Zambrano, Betzana; Dayan, Gustavo H.

2012-01-01

Dengue is a viral disease usually transmitted by Aedes aegypti mosquitoes. Dengue outbreaks in the Americas reported in medical literature and to the Pan American Health Organization are described. The outbreak history from 1600 to 2010 was categorized into four phases: Introduction of dengue in the Americas (1600–1946); Continental plan for the eradication of the Ae. aegypti (1947–1970) marked by a successful eradication of the mosquito in 18 continental countries by 1962; Ae. aegypti reinfestation (1971–1999) caused by the failure of the mosquito eradication program; Increased dispersion of Ae. aegypti and dengue virus circulation (2000–2010) characterized by a marked increase in the number of outbreaks. During 2010 > 1.7 million dengue cases were reported, with 50,235 severe cases and 1,185 deaths. A dramatic increase in the number of outbreaks has been reported in recent years. Urgent global action is needed to avoid further disease spread. PMID:23042846

Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity.

PubMed

Lee, Linda K; Gan, Victor C; Lee, Vernon J; Tan, Adriana S; Leo, Yee Sin; Lye, David C

2012-01-01

Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT ≥ 1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue. We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT ≥ 1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve=0.62; 95% confidence interval [CI]: 0.57-0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve=0.56; 95% CI: 0.52-0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF. Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.

Factors determining dengue outbreak in Malaysia.

PubMed

Ahmad, Rohani; Suzilah, Ismail; Wan Najdah, Wan Mohamad Ali; Topek, Omar; Mustafakamal, Ibrahim; Lee, Han Lim

2018-01-01

A large scale study was conducted to elucidate the true relationship among entomological, epidemiological and environmental factors that contributed to dengue outbreak in Malaysia. Two large areas (Selayang and Bandar Baru Bangi) were selected in this study based on five consecutive years of high dengue cases. Entomological data were collected using ovitraps where the number of larvae was used to reflect Aedes mosquito population size; followed by RT-PCR screening to detect and serotype dengue virus in mosquitoes. Notified cases, date of disease onset, and number and type of the interventions were used as epidemiological endpoint, while rainfall, temperature, relative humidity and air pollution index (API) were indicators for environmental data. The field study was conducted during 81 weeks of data collection. Correlation and Autoregressive Distributed Lag Model were used to determine the relationship. The study showed that, notified cases were indirectly related with the environmental data, but shifted one week, i.e. last 3 weeks positive PCR; last 4 weeks rainfall; last 3 weeks maximum relative humidity; last 3 weeks minimum and maximum temperature; and last 4 weeks air pollution index (API), respectively. Notified cases were also related with next week intervention, while conventional intervention only happened 4 weeks after larvae were found, indicating ample time for dengue transmission. Based on a significant relationship among the three factors (epidemiological, entomological and environmental), estimated Autoregressive Distributed Lag (ADL) model for both locations produced high accuracy 84.9% for Selayang and 84.1% for Bandar Baru Bangi in predicting the actual notified cases. Hence, such model can be used in forestalling dengue outbreak and acts as an early warning system. The existence of relationships among the entomological, epidemiological and environmental factors can be used to build an early warning system for the prediction of dengue outbreak so

Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living in Bandung, West Java, Indonesia.

PubMed

Porter, Kevin R; Beckett, Charmagne G; Kosasih, Herman; Tan, Ratna Irsiana; Alisjahbana, Bachti; Rudiman, Pandji Irani Fianza; Widjaja, Susana; Listiyaningsih, Erlin; Ma'Roef, Chairin Nisa; McArdle, James L; Parwati, Ida; Sudjana, Primal; Jusuf, Hadi; Yuwono, Djoko; Wuryadi, Suharyono

2005-01-01

A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted in a cohort of adult volunteers from two textile factories located in West Java, Indonesia. Volunteers in the cohort were bled every three months and were actively followed for the occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In areas where no symptomatic cases were detected, the incidence of asymptomatic or mild infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype identified, but all four serotypes were detected among the cohort. Four cases of DHF and one case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of a longitudinal cohort study of naturally acquired DF and DHF in adults.

Characterization of two anti-dengue human monoclonal antibodies prepared from PBMCs of patients with dengue illness in Thailand.

PubMed

Li, Z-Y; Yamashita, A; Kawashita, N; Sasaki, T; Pan, Y; Ono, K-I; Ikuta, K; Li, Y-G

2016-06-01

The global spread of the four dengue virus (DENV) serotypes (dengue-1 to -4) has made this virus a major and growing public health concern. Generally, pre-existing neutralizing antibodies derived from primary infection play a significant role in protecting against subsequent infection with the same serotype. By contrast, these pre-existing antibodies are believed to mediate a non-protective response to subsequent heterotypic DENV infections, leading to the onset of dengue illness. In this study, two monoclonal antibodies prepared by using peripheral blood mononuclear cells (PBMCs) from patients with dengue fever were characterized. Epitope mapping revealed that amino acid residues 254-278 in domain II of the viral envelope protein E were the target region of these antibodies. A database search revealed that certain sequences in this epitope region showed high conservation among the four serotypes of DENV. These two human monoclonal antibodies could neutralize DENV-2,-4 more effectively than DENV-1,-3. The amino acid sequences could not explain this difference in neutralizing activity. However, the 3D structure results showed that amino acid 274 could be the critical residue for the difference in neutralization. These results may provide basic information for the development of a dengue vaccine.

[Epidemiology of dengue fever in China since 1978].

PubMed

Xiong, Yiquan; Chen, Qing

2014-12-01

Since 1978, dengue fever occurred endemically and epidemically every 4 to 7 years in China, affecting commonly people aged between 20 and 60 years with similar incidences in males and females. Four serotypes of dengue virus have been identified in China, with DENV-1 as the predominant serotype. The incidence of dengue fever became gradually decreased after 1997 but increased significantly in the recent two years, especially in 2014, where, up to November, a total of 44894 cases had been reported in Guangdong Province. In this review, the authors summarize the epidemiology, geographical and population distribution of dengue fever in China since 1978 and analyze the factors contributing to the outbreak in 2014.

Identification of natural antimicrobial agents to treat dengue infection: In vitro analysis of latarcin peptide activity against dengue virus.

PubMed

Rothan, Hussin A; Bahrani, Hirbod; Rahman, Noorsaadah Abd; Yusof, Rohana

2014-05-31

Although there have been considerable advances in the study of dengue virus, no vaccines or anti-dengue drugs are currently available for humans. Therefore, new approaches are necessary for the development of potent anti-dengue drugs. Natural antimicrobial peptides (AMPs) with potent antiviral activities are potential hits-to-leads for antiviral drug discovery. We performed this study to identify and characterise the inhibitory potential of the latarcin peptide (Ltc 1, SMWSGMWRRKLKKLRNALKKKLKGE) against dengue virus replication in infected cells. The Ltc 1 peptide showed a significantly inhibitory effect against the dengue protease NS2B-NS3pro at 37°C, a physiological human temperature, (IC50, 12.68 ± 3.2 μM), and greater inhibitory effect was observed at 40°C, a temperature similar to a high fever (IC50, 6.58 ± 4.1 μM). A greater reduction in viral load (p.f.u./ml) was observed at simultaneous (0.7 ± 0.3 vs. 7.2 ± 0.5 control) and post-treatment (1.8 ± 0.7 vs. 6.8 ± 0.6 control) compared to the pre-treatment (4.5 ± 0.6 vs. 6.9 ± 0.5 control). Treatment with the Ltc 1 peptide reduced the viral RNA in a dose-dependent manner with EC50 values of 8.3 ± 1.2, 7.6 ± 2.7 and 6.8 ± 2.5 μM at 24, 48 and 72 h, respectively. The Ltc 1 peptide exhibited significant inhibitory effects against dengue NS2B-NS3pro and virus replication in the infected cells. Therefore, further investigation is necessary to develop the Ltc 1 peptide as a new anti-dengue therapeutic.

Dengue in the elderly: a review.

PubMed

Lin, Ray Junhao; Lee, Tau Hong; Leo, Yee Sin

2017-08-01

Changing dengue epidemiological trends have resulted in a shift in the disease burden to the adult population. Older adults suffer from poorer outcomes as compared to their younger counterparts, making clinical management of this sub-population particularly challenging. Areas covered: We present a review of the current literature on the changing epidemiology of dengue in the elderly, the atypical features of the clinical disease in this population with emphasis on severe disease presentations and challenges in the current management strategies. Expert commentary: Dengue in the elderly is an increasingly important yet greatly understudied area. There is an urgent need to refine the current diagnostic criteria to improve diagnosis, classification of disease severity and identify individuals in this population who are likely to progress to severe disease. Management strategies in this population would have to be adjusted to account for the increased number of co-morbidities. The role of the available dengue vaccines in this group is uncertain, and more studies into their safety and efficacy are critically needed.

The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae. aegypti strains and against multiple dengue virus serotypes

PubMed Central

Ramirez, Jose L.; Dimopoulos, George

2010-01-01

Dengue virus has become one of the most important arboviral pathogens affecting the world today. The virus is transmitted among humans by the mosquitoes Aedes aegypti and Ae. albopictus. Like other vector-borne pathogens, this virus encounters innate immune defenses within the mosquito vector that limit infection. We have previously demonstrated the involvement of the Toll pathway in the anti-dengue defense at 7 days after infection. In the present study, we have investigated the activity of this immune signaling pathway against different dengue virus serotypes at the early stages of infection in laboratory and field-derived mosquito strains. Our studies corroborate the importance of the Toll pathway in the anti-dengue defense repertoire at 3 days after an infectious blood meal, when new virions are released from the midgut for dissemination and infection of other mosquito tissues. These immune defenses are furthermore conserved among different Ae. aegypti strains and can act against a broad range of dengue virus serotypes. PMID:20079370

Dengue on islands: a Bayesian approach to understanding the global ecology of dengue viruses.

PubMed

Feldstein, Leora R; Brownstein, John S; Brady, Oliver J; Hay, Simon I; Johansson, Michael A

2015-05-01

Transmission of dengue viruses (DENV), the most common arboviral pathogens globally, is influenced by many climatic and socioeconomic factors. However, the relative contributions of these factors on a global scale are unclear. We randomly selected 94 islands stratified by socioeconomic and geographic characteristics. With a Bayesian model, we assessed factors contributing to the probability of islands having a history of any dengue outbreaks and of having frequent outbreaks. Minimum temperature was strongly associated with suitability for DENV transmission. Islands with a minimum monthly temperature of greater than 14.8°C (95% CI: 12.4-16.6°C) were predicted to be suitable for DENV transmission. Increased population size and precipitation were associated with increased outbreak frequency, but did not capture all of the variability. Predictions for 48 testing islands verified these findings. This analysis clarified two key components of DENV ecology: minimum temperature was the most important determinant of suitability; and endemicity was more likely in areas with high precipitation and large, but not necessarily dense, populations. Wealth and connectivity, in contrast, had no discernable effects. This model adds to our knowledge of global determinants of dengue risk and provides a basis for understanding the ecology of dengue endemicity. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Antibody-dependent enhancement of severe dengue disease in humans*

PubMed Central

Katzelnick, Leah C.; Gresh, Lionel; Halloran, M. Elizabeth; Mercado, Juan Carlos; Kuan, Guillermina; Gordon, Aubree; Balmaseda, Angel; Harris, Eva

2018-01-01

For dengue viruses (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models. Although suspected, such antibody-dependent enhancement (ADE) of severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of severe dengue disease is highest within a narrow range of pre-existing anti-DENV antibody titers. By contrast, we observe protection from all symptomatic dengue disease at high antibody titers. Thus, immune correlates of severe dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern. PMID:29097492

Performance of commercial dengue NS1 ELISA and molecular analysis of NS1 gene of dengue viruses obtained during surveillance in Indonesia.

PubMed

Aryati, Aryati; Trimarsanto, Hidayat; Yohan, Benediktus; Wardhani, Puspa; Fahri, Sukmal; Sasmono, R Tedjo

2013-12-29

Early diagnosis of dengue infection is crucial for better management of the disease. Diagnostic tests based on the detection of dengue virus (DENV) Non Structural Protein 1 (NS1) antigen are commercially available with different sensitivities and specificities observed in various settings. Dengue is endemic in Indonesia and clinicians are increasingly using the NS1 detection for dengue confirmation. This study described the performance of Panbio Dengue Early NS1 and IgM Capture ELISA assays for dengue detection during our surveillance in eight cities in Indonesia as well as the genetic diversity of DENV NS1 genes and its relationship with the NS1 detection. The NS1 and IgM/IgG ELISA assays were used for screening and confirmation of dengue infection during surveillance in 2010-2012. Collected serum samples (n = 440) were subjected to RT-PCR and virus isolation, in which 188 samples were confirmed for dengue infection. The positivity of the ELISA assays were correlated with the RT-PCR results to obtain the sensitivity of the assays. The NS1 genes of 48 Indonesian virus isolates were sequenced and their genetic characteristics were studied. Using molecular data as gold standard, the sensitivity of NS1 ELISA assay for samples from Indonesia was 56.4% while IgM ELISA was 73.7%. When both NS1 and IgM results were combined, the sensitivity increased to 89.4%. The NS1 sensitivity varied when correlated with city/geographical origins and DENV serotype, in which the lowest sensitivity was observed for DENV-4 (19.0%). NS1 sensitivity was higher in primary (67.6%) compared to secondary infection (48.2%). The specificity of NS1 assay for non-dengue samples were 100%. The NS1 gene sequence analysis of 48 isolates revealed the presence of polymorphisms of the NS1 genes which apparently did not influence the NS1 sensitivity. We observed a relatively low sensitivity of NS1 ELISA for dengue detection on RT-PCR-positive dengue samples. The detection rate increased significantly

A brief review on dengue molecular virology, diagnosis, treatment and prevalence in Pakistan

PubMed Central

2012-01-01

Dengue virus infection is a serious health problem infecting 2.5 billion people worldwide. Dengue is now endemic in more than 100 countries, including Pakistan. Each year hundreds of people get infected with dengue in Pakistan. Currently, there is no vaccine available for the prevention of Dengue virus infection due to four viral serotypes. Dengue infection can cause death of patients in its most severity, meanwhile many antiviral compounds are being tested against dengue virus infection to eradicate this disease but still there is a need to develop an efficient, low-cost and safe vaccine that can target all the four serotypes of dengue virus. This review summarizes dengue molecular virology, important drug targets, prevalence in Pakistan, diagnosis, treatment and medicinal plant inhibitors against dengue. PMID:22929369

Surface water areas significantly impacted 2014 dengue outbreaks in Guangzhou, China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Huaiyu; Huang, Shanqian

Dengue transmission in urban areas is strongly influenced by a range of biological and environmental factors, yet the key drivers still need further exploration. To better understand mechanisms of environment–mosquito–urban dengue transmission, we propose an empirical model parameterized and cross-validated from a unique dataset including viral gene sequences, vector dynamics and human dengue cases in Guangzhou, China, together with a 36-year urban environmental change maps investigated by spatiotemporal satellite image fusion. The dengue epidemics in Guangzhou are highly episodic and were not associated with annual rainfall over time. Our results indicate that urban environmental changes, especially variations in surface areamore » covered by water in urban areas, can substantially alter the virus population and dengue transmission. The recent severe dengue outbreaks in Guangzhou may be due to the surge in an artificial lake construction, which could increase infection force between vector (mainly Aedes albopictus) and host when urban water area significantly increased. Impacts of urban environmental change on dengue dynamics may not have been thoroughly investigated in the past studies and more work needs to be done to better understand the consequences of urbanization processes in our changing world. - Highlights: • Urban dengue outbreak is associated with water area in Guangzhou, 1978–2014. • Surface water area can alter population size of dengue virus in urban area. • Urban dengue outbreak is not associated with annual rainfall in Guangzhou. • Spatiotemporal satellite image fusion can investigate urban environmental change. • Urban environmental change could induce virus, vector, and dengue epidemic change.« less

The influence of climate variables on dengue in Singapore.

PubMed

Pinto, Edna; Coelho, Micheline; Oliver, Leuda; Massad, Eduardo

2011-12-01

In this work we correlated dengue cases with climatic variables for the city of Singapore. This was done through a Poisson Regression Model (PRM) that considers dengue cases as the dependent variable and the climatic variables (rainfall, maximum and minimum temperature and relative humidity) as independent variables. We also used Principal Components Analysis (PCA) to choose the variables that influence in the increase of the number of dengue cases in Singapore, where PC₁ (Principal component 1) is represented by temperature and rainfall and PC₂ (Principal component 2) is represented by relative humidity. We calculated the probability of occurrence of new cases of dengue and the relative risk of occurrence of dengue cases influenced by climatic variable. The months from July to September showed the highest probabilities of the occurrence of new cases of the disease throughout the year. This was based on an analysis of time series of maximum and minimum temperature. An interesting result was that for every 2-10°C of variation of the maximum temperature, there was an average increase of 22.2-184.6% in the number of dengue cases. For the minimum temperature, we observed that for the same variation, there was an average increase of 26.1-230.3% in the number of the dengue cases from April to August. The precipitation and the relative humidity, after analysis of correlation, were discarded in the use of Poisson Regression Model because they did not present good correlation with the dengue cases. Additionally, the relative risk of the occurrence of the cases of the disease under the influence of the variation of temperature was from 1.2-2.8 for maximum temperature and increased from 1.3-3.3 for minimum temperature. Therefore, the variable temperature (maximum and minimum) was the best predictor for the increased number of dengue cases in Singapore.

AfroColombian ethnicity, a paradoxical protective factor against Dengue

PubMed Central

Alzate, Alberto; Martínez Romero, Héctor Jairo; Concha-Eastman, Alberto Ignacio

2016-01-01

Introduction: Dengue is a priority public health problem. During epidemics in Cuba and Haiti, ethnic African descendant population had lower risk of dengue, and the ethnic factor was proposed as a protective one. Objective: To determine the relation between the Dengue's cumulative incidence and the Afro-Colombian proportion in communities of Cali, during the epidemic of 2013. Methods: This study was conducted in Cali, Colombia. The design was ecological, using information from the National Census 2005 projected to 2013, from the National Administrative Department of Statistics (DANE), and the National Epidemiological Surveillance System. It was obtained the Pearson´s correlation coefficient between cumulative incidence and the proportion of Afro-Colombian population by communities. Additionally, the cumulative incidences of dengue were evaluated in two zones with different proportion of Afro-Colombian population. The association was also evaluated for aggregation bias, confounding by social variables, and interaction by area of ​​residence. Results: Dengue´s cumulative incidence was significantly lower for Afro-Colombians regardless of the proportion of Afro-Colombian population in the area of residence. The relative risk of dengue between non-Afro-Colombians and Afro-Colombians was 9.4 (95% CI=8.4-10.6) in zones with high proportion of Afro-Colombian population, while the relative risk of dengue was 4.0 (95% CI :3.6 - 4.4) in the zone with lower proportion of Afro-Colombian population. There was no evidence of aggregation bias or confounding in the association by social variables. Conclusions: The Afro-Colombian population had a significantly lower risk of getting dengue and its complications, compared with the non-Afro-Colombian population. The non-Afro-Colombian populations living in areas with a high proportion of Afro-Colombians increase their risk of dengue more than double, suggesting an asymptomatic viremic environment. PMID:27821892

AfroColombian ethnicity, a paradoxical protective factor against Dengue.

PubMed

Rojas Palacios, Jorge Humberto; Alzate, Alberto; Martínez Romero, Héctor Jairo; Concha-Eastman, Alberto Ignacio

2016-09-30

Dengue is a priority public health problem. During epidemics in Cuba and Haiti, ethnic African descendant population had lower risk of dengue, and the ethnic factor was proposed as a protective one. To determine the relation between the Dengue's cumulative incidence and the Afro-Colombian proportion in communities of Cali, during the epidemic of 2013. This study was conducted in Cali, Colombia. The design was ecological, using information from the National Census 2005 projected to 2013, from the National Administrative Department of Statistics (DANE), and the National Epidemiological Surveillance System. It was obtained the Pearson´s correlation coefficient between cumulative incidence and the proportion of Afro-Colombian population by communities. Additionally, the cumulative incidences of dengue were evaluated in two zones with different proportion of Afro-Colombian population. The association was also evaluated for aggregation bias, confounding by social variables, and interaction by area of ​​residence. Dengue´s cumulative incidence was significantly lower for Afro-Colombians regardless of the proportion of Afro-Colombian population in the area of residence. The relative risk of dengue between non-Afro-Colombians and Afro-Colombians was 9.4 (95% CI=8.4-10.6) in zones with high proportion of Afro-Colombian population, while the relative risk of dengue was 4.0 (95% CI :3.6 - 4.4) in the zone with lower proportion of Afro-Colombian population. There was no evidence of aggregation bias or confounding in the association by social variables. The Afro-Colombian population had a significantly lower risk of getting dengue and its complications, compared with the non-Afro-Colombian population. The non-Afro-Colombian populations living in areas with a high proportion of Afro-Colombians increase their risk of dengue more than double, suggesting an asymptomatic viremic environment.

Seroepidemiology of dengue in travellers: a paired sera analysis.

PubMed

Leder, Karin; Mutsch, Margot; Schlagenhauf, Patricia; Luxemburger, Christine; Torresi, Joseph

2013-01-01

Dengue is a frequent cause of fever in travellers. The true extent is unknown as many infections are asymptomatic or undiagnosed. We used paired sera, with pre- and post-travel specimens from Swiss travellers to tropical destinations, to evaluate the seroepidemiology of travel-related dengue. Post-travel specimens were tested for the presence of IgG and IgM antibodies to dengue antigen serotypes (1, 2, 3 and 4) using an indirect enzyme-linked immunosorbent assay (ELISA). All post-travel sera that screened as positive for dengue IgG or IgM antibodies were re-tested with the corresponding pre-travel sera as paired assays in order to detect seroconversion. There were 285 travellers with specimens available for analysis. Two hundred and fifty seven of the 285 individuals (90.2%) had negative dengue serology post-travel. Of the remaining 28 cases, 25 were dengue IgG positive and 3 had equivocal results. This corresponds to IgG seropositivity in 8.9%. Eighteen of these 25 individuals had a pre-travel specimen available for testing, of which 15 were positive for IgG consistent with possible past exposure. Three of the 18 had negative serology pre-travel, indicating possible recent infection. This corresponds to an attack rate of possible dengue of 1.1% and an incidence rate of 6.7 per 1000 person-months (95% CI 0-60.0). Two of these three individuals had received yellow fever vaccine for their trip, raising the potential of cross-reactivity. The confirmed dengue attack rate therefore was 0.23% with a corresponding incidence rate of 2.2 per 1000 person-months (95% CI-0-33.1). Seroepidemiology provides additional evidence of an appreciable risk of acute dengue infection among travellers to tropical destinations. Copyright © 2013. Published by Elsevier Ltd.

Screening of antiviral activities in medicinal plants extracts against dengue virus using dengue NS2B-NS3 protease assay.

PubMed

Rothan, H A; Zulqarnain, M; Ammar, Y A; Tan, E C; Rahman, N A; Yusof, R

2014-06-01

Dengue virus infects millions of people worldwide and there is no vaccine or anti-dengue therapeutic available. Screening large numbers of medicinal plants for anti-dengue activities is an alternative strategy in order to find the potent therapeutic compounds. Therefore, this study was designed to identify anti-dengue activities in nineteen medicinal plant extracts that are used in traditional medicine. Local medicinal plants Vernonia cinerea, Hemigraphis reptans, Hedyotis auricularia, Laurentia longiflora, Tridax procumbers and Senna angustifolia were used in this study. The highest inhibitory activates against dengue NS2B-NS3pro was observed in ethanolic extract of S. angustifolia leaves, methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems. These findings were further verified by in vitro viral inhibition assay. Methanolic extract of V. cinerea leaves, ethanol extract of T. procumbens stems and at less extent ethanolic extract of S. angustifolia leaves were able to maintain the normal morphology of DENV2-infected Vero cells without causing much cytopathic effects (CPE). The percentage of viral inhibition of V. cinerea and T. procumbens extracts were significantly higher than S. angustifolia extract as measured by plaque formation assay and RT-qPCR. In conclusion, The outcome of this study showed that the methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems possessed high inhibitory activates against dengue virus that worth more investigation.

Risk factors associated with an outbreak of dengue fever/dengue haemorrhagic fever in Hanoi, Vietnam.

PubMed

Toan, D T T; Hoat, L N; Hu, W; Wright, P; Martens, P

2015-06-01

Dengue fever/dengue haemorrhagic fever (DF/DHF) appears to be emerging in Hanoi in recent years. A case-control study was performed to investigate risk factors for the development of DF/DHF in Hanoi. A total of 73 patients with DF/DHF and 73 control patients were included in the study. The risk factor analysis indicated that living in rented housing, living near uncovered sewers, and living in a house discharging sewage directly into to ponds were all significantly associated with DF/DHF. People living in rented houses were 2·2 times more at risk of DF/DHF than those living in their own homes [adjusted odds ratio (aOR) 2·2, 95% confidence interval (CI) 1·1-4·6]. People living in an unhygienic house, or in a house discharging sewage directly to the ponds were 3·4 times and 4·3 times, respectively, more likely to be associated with DF/DHF (aOR 3·4, 95% CI 1-11·7; aOR 4·3, 95% CI 1·1-16·9). These results contribute to the understanding of the dynamics of dengue transmission in Hanoi, which is needed to implement dengue prevention and control programmes effectively and efficiently.

Immune reactivity to dengue and Aedes albopictus mosquitoes in the population from Macao, China, before dengue occurrence.

PubMed

De Carvalho, Isabel Lopes; Rocha, Diara Kady; Almeida, A Paulo G

2011-01-01

A serological survey was conducted in Macao, China, in 753 individuals, with the objective of looking for antibodies to the mosquito, Aedes albopictus (Skuse 1894) (Diptera: Culicidae), and to dengue, before the occurrence of any autochthonous dengue cases. Blood samples were collected at several public health services, a questionnaire was answered, and enzyme-linked immunosorbant assay (ELISA) and Western blot techniques were performed with extracts of mosquito head and thorax (HT). Anti-Aedes albopictus IgG antibodies were present in titres 1:10(2)-1:10(3) in 9%, and in titres 1:10(4)-1:10(5) in 42% of the sera tested. This reactivity was more frequent (59%) in the population which had resided only in Macao in the 2 years previous to the survey, as opposed to those that had also resided in other areas (50%). From the 230 reactive sera selected for immunoblot, 48 (21%) reacted with a wide range of proteins from above 224 kDa to 21 kDa, with different patterns according to individual sera. Proteins in the intervals 35.3-28.7 kDa and 28.7-21.1 kDa were labelled by the greatest number of sera, 15 and 19 respectively. The presence of anti-Aedes albopictus antibodies presented a statistical relation to skin reaction to mosquito bites, but immunoblot patterns did not. Anti-dengue IgG antibodies were found in 48% of the subjects, with a higher proportion in people who had resided out of Macao, or who were nationals from dengue-endemic neighboring countries. Anti-dengue reactivity was in agreement with anti-mosquito reactivity in half of the population. It would be interesting to see if this proportion has changed since dengue became endemic in Macao in 2001.

Economic cost and burden of dengue in the Philippines.

PubMed

Edillo, Frances E; Halasa, Yara A; Largo, Francisco M; Erasmo, Jonathan Neil V; Amoin, Naomi B; Alera, Maria Theresa P; Yoon, In-Kyu; Alcantara, Arturo C; Shepard, Donald S

2015-02-01

Dengue, the world's most important mosquito-borne viral disease, is endemic in the Philippines. During 2008-2012, the country's Department of Health reported an annual average of 117,065 dengue cases, placing the country fourth in dengue burden in southeast Asia. This study estimates the country's annual number of dengue episodes and their economic cost. Our comparison of cases between active and passive surveillance in Punta Princesa, Cebu City yielded an expansion factor of 7.2, close to the predicted value (7.0) based on the country's health system. We estimated an annual average of 842,867 clinically diagnosed dengue cases, with direct medical costs (in 2012 US dollars) of $345 million ($3.26 per capita). This is 54% higher than an earlier estimate without Philippines-specific costs. Ambulatory settings treated 35% of cases (representing 10% of direct costs), whereas inpatient hospitals served 65% of cases (representing 90% of direct costs). The economic burden of dengue in the Philippines is substantial. © The American Society of Tropical Medicine and Hygiene.

Next-generation dengue vaccines: novel strategies currently under development.

PubMed

Durbin, Anna P; Whitehead, Stephen S

2011-10-01

Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.

Typhoid and dengue coinfection: case reports.

PubMed

Bansal, Rohit; Bansal, Priya; Tomar, Laxmikant Ramkumarsingh

2015-01-01

Both dengue and typhoid fever have emerged as major public health problems in India. Coinfection with both these diseases is rarely reported. Here we report two confirmed cases of concurrent illness of dengue with typhoid fever; both patients were managed as outpatients and recovered completely. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Approaches to Refining Estimates of Global Burden and Economics of Dengue

PubMed Central

Shepard, Donald S.; Undurraga, Eduardo A.; Betancourt-Cravioto, Miguel; Guzmán, María G.; Halstead, Scott B.; Harris, Eva; Mudin, Rose Nani; Murray, Kristy O.; Tapia-Conyer, Roberto; Gubler, Duane J.

2014-01-01

Dengue presents a formidable and growing global economic and disease burden, with around half the world's population estimated to be at risk of infection. There is wide variation and substantial uncertainty in current estimates of dengue disease burden and, consequently, on economic burden estimates. Dengue disease varies across time, geography and persons affected. Variations in the transmission of four different viruses and interactions among vector density and host's immune status, age, pre-existing medical conditions, all contribute to the disease's complexity. This systematic review aims to identify and examine estimates of dengue disease burden and costs, discuss major sources of uncertainty, and suggest next steps to improve estimates. Economic analysis of dengue is mainly concerned with costs of illness, particularly in estimating total episodes of symptomatic dengue. However, national dengue disease reporting systems show a great diversity in design and implementation, hindering accurate global estimates of dengue episodes and country comparisons. A combination of immediate, short-, and long-term strategies could substantially improve estimates of disease and, consequently, of economic burden of dengue. Suggestions for immediate implementation include refining analysis of currently available data to adjust reported episodes and expanding data collection in empirical studies, such as documenting the number of ambulatory visits before and after hospitalization and including breakdowns by age. Short-term recommendations include merging multiple data sources, such as cohort and surveillance data to evaluate the accuracy of reporting rates (by health sector, treatment, severity, etc.), and using covariates to extrapolate dengue incidence to locations with no or limited reporting. Long-term efforts aim at strengthening capacity to document dengue transmission using serological methods to systematically analyze and relate to epidemiologic data. As promising tools

Approaches to refining estimates of global burden and economics of dengue.

PubMed

Shepard, Donald S; Undurraga, Eduardo A; Betancourt-Cravioto, Miguel; Guzmán, María G; Halstead, Scott B; Harris, Eva; Mudin, Rose Nani; Murray, Kristy O; Tapia-Conyer, Roberto; Gubler, Duane J

2014-11-01

Dengue presents a formidable and growing global economic and disease burden, with around half the world's population estimated to be at risk of infection. There is wide variation and substantial uncertainty in current estimates of dengue disease burden and, consequently, on economic burden estimates. Dengue disease varies across time, geography and persons affected. Variations in the transmission of four different viruses and interactions among vector density and host's immune status, age, pre-existing medical conditions, all contribute to the disease's complexity. This systematic review aims to identify and examine estimates of dengue disease burden and costs, discuss major sources of uncertainty, and suggest next steps to improve estimates. Economic analysis of dengue is mainly concerned with costs of illness, particularly in estimating total episodes of symptomatic dengue. However, national dengue disease reporting systems show a great diversity in design and implementation, hindering accurate global estimates of dengue episodes and country comparisons. A combination of immediate, short-, and long-term strategies could substantially improve estimates of disease and, consequently, of economic burden of dengue. Suggestions for immediate implementation include refining analysis of currently available data to adjust reported episodes and expanding data collection in empirical studies, such as documenting the number of ambulatory visits before and after hospitalization and including breakdowns by age. Short-term recommendations include merging multiple data sources, such as cohort and surveillance data to evaluate the accuracy of reporting rates (by health sector, treatment, severity, etc.), and using covariates to extrapolate dengue incidence to locations with no or limited reporting. Long-term efforts aim at strengthening capacity to document dengue transmission using serological methods to systematically analyze and relate to epidemiologic data. As promising tools

Evaluation of single-round infectious, chimeric dengue type 1 virus as an antigen for dengue functional antibody assays.

PubMed

Yamanaka, Atsushi; Suzuki, Ryosuke; Konishi, Eiji

2014-07-23

Dengue fever and dengue hemorrhagic fever are endemic throughout tropical and subtropical countries. Four serotypes of dengue viruses (DENV-1 to DENV-4), each with several genotypes including various subclades, are co-distributed in most endemic areas. Infection-neutralizing and -enhancing antibodies are believed to play protective and pathogenic roles, respectively. Measurement of these functional antibodies against a variety of viral strains is thus important for evaluating coverage and safety of dengue vaccine candidates. Although transportation of live virus materials beyond national borders is increasingly limited, this difficulty may be overcome using biotechnology that enables generation of an antibody-assay antigen equivalent to authentic virus based on viral sequence information. A rapid system to produce flavivirus single-round infectious particles (SRIPs) was recently developed using a Japanese encephalitis virus (JEV) subgenomic replicon plasmid. This system allows production of chimeric SRIPs that have surface proteins of other flaviviruses. In the present study, SRIPs of DENV-1 (D1-SRIPs) were evaluated as an antigen for functional antibody assays. Inclusion of the whole mature capsid gene of JEV into the replicon plasmid provided higher D1-SRIP yields than did its exclusion in cases where a DENV-1 surface-protein-expressing plasmid was used for co-transfection of 293T cells with the replicon plasmid. In an assay to measure the balance between neutralizing and enhancing activities, dose (antibody dilution)-dependent activity curves in dengue-immune human sera or mouse monoclonal antibodies obtained using D1-SRIP antigen were equivalent to those obtained using DENV-1 antigen. Similar results were obtained using additional DENV-2 and DENV-3 systems. In a conventional Vero-cell neutralization test, a significant correlation was shown between antibody titers obtained using D1-SRIP and DENV-1 antigens. These results demonstrate the utility of D1-SRIPs as

Dengue and Chikungunya Vector Control Pocket Guide

USDA-ARS?s Scientific Manuscript database

This technical guide consolidates information and procedures for surveillance and control of mosquitoes that transmit dengue and chikungunya viruses. The guide focuses on mosquitoes that transmit dengue but also makes reference to chikungunya and yellow fever because the pathogens that cause these ...

Change in Dengue and Japanese Encephalitis Seroprevalence Rates in Sri Lanka

PubMed Central

Jeewandara, Chandima; Gomes, Laksiri; Paranavitane, S. A.; Tantirimudalige, Mihiri; Panapitiya, Sumedha Sandaruwan; Jayewardene, Amitha; Fernando, Samitha; Fernando, R. H.; Prathapan, Shamini

2015-01-01

Background Sri Lanka has been affected by epidemics of dengue infections for many decades and the incidence and severity of dengue infections have been rising each year. Therefore, we investigated the age stratified seroprevalence of dengue infections in order to facilitate future dengue vaccine strategies. In addition, since the symptomatic dengue infections have increased during the past few decades, we also investigated the possible association with Japanese Encephalitis Virus (JEV) antibody seropositivity with symptomatic dengue in a community cohort in Sri Lanka. Methods 1689 healthy individuals who were attending a primary health care facility were recruited. Dengue and JEV antibody status was determined in all individuals and JEV vaccination status was recorded. Results 1152/1689 (68.2%) individuals were seropositive for dengue and only 133/1152 (11.5%) of them had been hospitalized to due to dengue. A significant and positive correlation was observed for dengue antibody seropositivity and age in children (Spearmans R = 0.84, p = 0.002) and in adults (Spearmans R = 0.96, p = 0.004). We observed a significant rise in the age stratified seroprevalence rates in children over a period of 12 years. For instance, in year 2003 the annual seroconversion rate was 1.5% per annum, which had risen to 3.79% per annum by 2014. We also found that both adults (p<0.001) and in children (p = 0.03) who were hospitalized due to dengue were more likely to be seropositive for JEV antibodies. However, 244 (91.4%) of adults who were seropositive for JEV had not had the JEV vaccine. Conclusions Dengue seroprevalence rates have risen significantly over the last 12 years in Sri Lanka, possibly due to increased transmission. As individuals who were hospitalized due to dengue were more likely to be seropositive for JEV, the possibility of cross-reactive assays and/or of JEV infection on immunity to the DENV and clinical disease severity should be further investigated. PMID:26696417

Distribution, seasonal variation & dengue transmission prediction in Sisaket, Thailand

PubMed Central

Wongkoon, S.; Jaroensutasinee, M.; Jaroensutasinee, K.

2013-01-01

Background & objectives: Environmental factors including weather variables may play a significant role in the transmission of dengue. This study investigated the effect of seasonal variation on the abundance of Aedes aegypti and Ae. albopictus larvae and explored the impact of weather variability on dengue transmission in Sisaket, Thailand. Methods: The monthly mosquito larval surveys were carried out in urban and rural areas in Sisaket, Thailand from January to December 2010. Data on monthly-reported cases of dengue fever over the period 2004-2010 were obtained from the Ministry of Public Health. Weather data over the same period were obtained from the Thai Meteorological Department. Chi-square test was used to find the differences relating to seasonal variability, areas of study, and mosquito species factors using entomological survey data. Time series Poisson regression analysis was performed using data on monthly weather variables and dengue cases. Results: There were more Ae. aegypti larvae per household than Ae. albopictus larvae in the winter and rainy seasons. More Aedes larvae per household were found in the rainy season than in the winter and summer seasons. Relative humidity at a lag of one month and rainy days in the current month were significant predictors of dengue incidence in Sisaket. Interpretation & conclusions: Increased rain during the current month and less humidity during the previous month might trigger a higher incidence of dengue epidemic in Sisaket. The present findings suggest that the dengue incidence corresponds with the number of Aedes larvae. The seasonal patterns of dengue outbreaks coincide with the rainy season. PMID:24135179

Using global maps to predict the risk of dengue in Europe.

PubMed

Rogers, David J; Suk, Jonathan E; Semenza, Jan C

2014-01-01

This article attempts to quantify the risk to Europe of dengue, following the arrival and spread there of one of dengue's vector species Aedes (Stegomyia) albopictus. A global risk map for dengue is presented, based on a global database of the occurrence of this disease, derived from electronic literature searches. Remotely sensed satellite data (from NASA's MODIS series), interpolated meteorological data, predicted distribution maps of dengue's two main vector species, Aedes aegypti and Aedes albopictus, a digital elevation surface and human population density data were all used as potential predictor variables in a non-linear discriminant analysis modelling framework. One hundred bootstrap models were produced by randomly sub-sampling three different training sets for dengue fever, severe dengue (i.e. dengue haemorrhagic fever, DHF) and all-dengue, and output predictions were averaged to produce a single global risk map for each type of dengue. This paper concentrates on the all-dengue models. Key predictor variables were various thermal data layers, including both day- and night-time Land Surface Temperature, human population density, and a variety of rainfall variables. The relative importance of each may be shown visually using rainbow files and quantitatively using a ranking system. Vegetation Index variables (a common proxy for humidity or saturation deficit) were rarely chosen in the models. The kappa index of agreement indicated an excellent (dengue haemorrhagic fever, Cohen's kappa=0.79 ± 0.028, AUC=0.96 ± 0.007) or good fit of the top ten models in each series to the data (Cohen's kappa=0.73 ± 0.018, AUC=0.94 ± 0.007 for dengue fever and 0.74 ± 0.017, AUC=0.95 ± 0.005 for all dengue). The global risk map predicts widespread dengue risk in SE Asia and India, in Central America and parts of coastal South America, but in relatively few regions of Africa. In many cases these are less extensive predictions than those of other published dengue risk maps

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

PubMed

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

2014-04-01

In this study, we evaluated the performance of a rapid test, the SD BIOLINE Dengue Duo (SD BDD) kit, with a panel of serum samples from 310 Mexican patients with diagnosis of dengue infection previously confirmed by reference enzyme-linked immunosorbent assay tests. Eighty-seven negative samples from other febrile illnesses were included as controls. The SD BDD showed an overall sensitivity of 90.65% and specificity of 89.66%. No statistically significant differences were found in the sensitivity of the SD BDD kit compared between primary or secondary infections (87.05% versus 93.57%, respectively, P = 0.0761) and dengue fever or dengue hemorrhagic fever cases (90.77% versus 89.74%, respectively, P = 0.7716). However, a higher sensitivity in the acute phase of dengue infection was found compared with the convalescent phase (93.03% versus 81.82%, respectively, P = 0.0089). These results indicate that the SD BDD kit is a useful tool to diagnose dengue infections, both in primary or secondary infections and mainly during the acute phase. Copyright © 2014 Elsevier Inc. All rights reserved.

Increased Levels of Txa2 Induced by Dengue Virus Infection in IgM Positive Individuals Is Related to the Mild Symptoms of Dengue

PubMed Central

Oliveira, Eneida S.; Colombarolli, Stella G.; Nascimento, Camila S.; Batista, Izabella C. A.; Ferreira, Jorge G. G.; Alvarenga, Daniele L. R.; de Sousa, Laís O. B.; Assis, Rafael R.; Rocha, Marcele N.; Alves, Érica A. R.; Calzavara-Silva, Carlos E.

2018-01-01

The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus-induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated. Dengue virus infection increases the levels of thromboxane A2 in IgM-positive individuals as well as the amount of lipid bodies in monocytes in IgM-negative individuals. We suggest that increased levels of thromboxane A2 in IgM-positive individuals plays a protective role against the development of severe symptoms of dengue, such as vascular leakage. PMID:29495587

First isolation of dengue virus from the 2010 epidemic in Nepal.

PubMed

Pandey, Basu D; Nabeshima, Takeshi; Pandey, Kishor; Rajendra, Saroj P; Shah, Yogendra; Adhikari, Bal R; Gupta, Govinda; Gautam, Ishan; Tun, Mya M N; Uchida, Reo; Shrestha, Mahendra; Kurane, Ichiro; Morita, Kouichi

2013-09-01

Dengue is an emerging disease in Nepal and was first observed as an outbreak in nine lowland districts in 2006. In 2010, however, a large epidemic of dengue occurred with 4,529 suspected and 917 serologically-confirmed cases and five deaths reported in government hospitals in Nepal. The collection of demographic information was performed along with an entomological survey and clinical evaluation of the patients. A total of 280 serum samples were collected from suspected dengue patients. These samples were subjected to routine laboratory investigations and IgM-capture ELISA for dengue serological identification, and 160 acute serum samples were used for virus isolation, RT-PCR, sequencing and phylogenetic analysis. The results showed that affected patients were predominately adults, and that 10% of the cases were classified as dengue haemorrhagic fever/ dengue shock syndrome. The genetic characterization of dengue viruses isolated from patients in four major outbreak areas of Nepal suggests that the DENV-1 strain was responsible for the 2010 epidemic. Entomological studies identified Aedes aegypti in all epidemic areas. All viruses belonged to a monophyletic single clade which is phylogenetically close to Indian viruses. The dengue epidemic started in the lowlands and expanded to the highland areas. To our knowledge, this is the first dengue isolation and genetic characterization reported from Nepal.

Dengue fever in a liver-transplanted patient: a case report.

PubMed

Weerakkody, Ranga Migara; Palangasinghe, Dhammika Randula; Dalpatadu, Kaluthanthri Patabandi Chamila; Rankothkumbura, Jeewan Pradeep; Cassim, Mohammed Rezni Nizam; Karunanayake, Panduka

2014-11-21

Dengue fever is one of the commonest mosquito-borne diseases in the tropics, and Sri Lanka is no exception. Despite its commonness, dengue fever has rarely been described among patients who have undergone transplantation. We report the case of a patient with dengue fever after liver transplantation, which, to the best of our knowledge, is the first such reported case outside Brazil. Our patient was a 46-year-old Sri Lakan man who presented to our institution two years after undergoing an ABO-compatible cadaveric liver transplant. At presentation, he had typical symptoms of dengue fever. He was taking prednisolone 5mg daily and tacrolimus 3mg twice daily as immunosuppression. Initial investigations showed thrombocytopenia and neutropenia that reached a nadir by day 7 of his illness. He had elevated liver enzymes as well. The diagnosis was confirmed on the basis of NS1 antigen detection by enzyme-linked immunosorbent assay. His blood cultures and polymerase chain reaction tests for cytomegalovirus were negative. He made an uneventful recovery and was discharged by day 9 of his illness. However, normalization of liver function took nearly two weeks. In three previously reported Brazilian cases of dengue after liver transplantation, the patients presented with dengue shock syndrome, in contrast to the relatively milder presentation of our patient. Because of the lack of case reports in the literature, it is difficult to ascertain the risk factors for severe dengue infection in transplants, but dengue fever reported in renal transplants sheds some light on them. High-dose steroids increase the risk of thrombocytopenia, whereas tacrolimus has been reported to prolong the duration of symptoms. Otherwise, dengue fever is a relatively mild illness in patients who have undergone renal transplantation, and renal allograft survival has been reported to be 86% following dengue fever. Dengue is a rarely reported infection in patients who have undergone transplantation. A high

Dengue Virus Serotypes 1 and 2 Responsible for Major Dengue Outbreaks in Nepal: Clinical, Laboratory, and Epidemiological Features

PubMed Central

Dumre, Shyam Prakash; Bhandari, Renu; Shakya, Geeta; Shrestha, Sanjaya Kumar; Cherif, Mahamoud Sama; Ghimire, Prakash; Klungthong, Chonticha; Yoon, In-Kyu; Hirayama, Kenji; Na-Bangchang, Kesara; Fernandez, Stefan

2017-01-01

Abstract. Dengue virus (DENV) is expanding toward previously nonendemic areas. DENV has recently been introduced in Nepal with limited information. We report the clinical features and serotype distribution of DENV in Nepal during the 2010 outbreaks. A total of 1,215 clinical dengue cases at two major hospitals of central and western Nepal were investigated. Demographic, clinical, and laboratory parameters were recorded. Serum specimens were tested for DENV by IgM/IgG enzyme-linked immunosorbent assays (ELISAs) and reverse transcription polymerase chain reaction (RT-PCR). We confirmed DENV infection in 403 (33%) patients from 12 districts with an estimated case fatality rate of 1.5%. DENV infection was more common in adults (87%) and urban settings (74%). We detected all four serotypes but DENV-1 and -2 were mainly responsible for major outbreaks (92%). Overall, 60% of all DENV infections were secondary and 17% were severe dengue; both being more frequent among the DENV-2 infections. Rash, bleeding, abdominal pain, hepatomegaly, elevated liver enzymes, and thrombocytopenia were significantly more common in severe dengue compared with nonsevere infections. We also confirmed the expansion of dengue to hill urban areas (DENV-1 and -2), including the capital Kathmandu (altitude, 1,300 m) though > 90% cases were from southern plains. Differential clinical and laboratory features probably help in clinical decisions. Multiple serotypes circulation and elevated secondary infections pose potential risk of severe outbreaks and deaths in the future. Therefore, a country with recent dengue introduction, like Nepal, urgently requires a systematic surveillance and appropriate control measures in place to respond to any disastrous outbreaks. PMID:29031282

First Experimental In Vivo Model of Enhanced Dengue Disease Severity through Maternally Acquired Heterotypic Dengue Antibodies

PubMed Central

Ng, Jowin Kai Wei; Zhang, Summer Lixin; Tan, Hwee Cheng; Yan, Benedict; Maria Martinez Gomez, Julia; Tan, Wei Yu; Lam, Jian Hang; Tan, Grace Kai Xin; Ooi, Eng Eong; Alonso, Sylvie

2014-01-01

Dengue (DEN) represents the most serious arthropod-borne viral disease. DEN clinical manifestations range from mild febrile illness to life-threatening hemorrhage and vascular leakage. Early epidemiological observations reported that infants born to DEN-immune mothers were at greater risk to develop the severe forms of the disease upon infection with any serotype of dengue virus (DENV). From these observations emerged the hypothesis of antibody-dependent enhancement (ADE) of disease severity, whereby maternally acquired anti-DENV antibodies cross-react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Although in vitro and in vivo experimental set ups have indirectly supported the ADE hypothesis, direct experimental evidence has been missing. Furthermore, a recent epidemiological study has challenged the influence of maternal antibodies in disease outcome. Here we have developed a mouse model of ADE where DENV2 infection of young mice born to DENV1-immune mothers led to earlier death which correlated with higher viremia and increased vascular leakage compared to DENV2-infected mice born to dengue naïve mothers. In this ADE model we demonstrated the role of TNF-α in DEN-induced vascular leakage. Furthermore, upon infection with an attenuated DENV2 mutant strain, mice born to DENV1-immune mothers developed lethal disease accompanied by vascular leakage whereas infected mice born to dengue naïve mothers did no display any clinical manifestation. In vitro ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice born to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice born to DENV1-immune mothers, thus reproducing epidemiological observations. Overall, this work provides direct in vivo demonstration of the role of maternally acquired heterotypic dengue antibodies in the enhancement of dengue

Unusual Dengue Virus 3 Epidemic in Nicaragua, 2009

PubMed Central

Gutierrez, Gamaliel; Standish, Katherine; Narvaez, Federico; Perez, Maria Angeles; Saborio, Saira; Elizondo, Douglas; Ortega, Oscar; Nuñez, Andrea; Kuan, Guillermina; Balmaseda, Angel; Harris, Eva

2011-01-01

The four dengue virus serotypes (DENV1–4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009–January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 dengue cases were recorded in 2009–10, compared to 13–65 cases in 2004–9. In both studies, significantly more patients experienced “compensated shock” (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse) in 2009–10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001) and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001). Signs of poor peripheral perfusion presented significantly earlier (1–2 days) in 2009–10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years – similar to the cohort study. DENV-3 predominated in 2008–9, 2009–10, and 2010–11, and full-length sequencing revealed no major genetic changes from 2008–9 to 2010–11. In 2008–9 and 2010–11, typical dengue was observed; only in 2009–10 was unusual presentation noted. Multivariate analysis revealed only “2009–10” as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1-2009 antibodies. This study demonstrates that

Spatiotemporal analysis of dengue fever in Nepal from 2010 to 2014.

PubMed

Acharya, Bipin Kumar; Cao, ChunXiang; Lakes, Tobia; Chen, Wei; Naeem, Shahid

2016-08-22

Due to recent emergence, dengue is becoming one of the major public health problems in Nepal. The numbers of reported dengue cases in general and the area with reported dengue cases are both continuously increasing in recent years. However, spatiotemporal patterns and clusters of dengue have not been investigated yet. This study aims to fill this gap by analyzing spatiotemporal patterns based on monthly surveillance data aggregated at district. Dengue cases from 2010 to 2014 at district level were collected from the Nepal government's health and mapping agencies respectively. GeoDa software was used to map crude incidence, excess hazard and spatially smoothed incidence. Cluster analysis was performed in SaTScan software to explore spatiotemporal clusters of dengue during the above-mentioned time period. Spatiotemporal distribution of dengue fever in Nepal from 2010 to 2014 was mapped at district level in terms of crude incidence, excess risk and spatially smoothed incidence. Results show that the distribution of dengue fever was not random but clustered in space and time. Chitwan district was identified as the most likely cluster and Jhapa district was the first secondary cluster in both spatial and spatiotemporal scan. July to September of 2010 was identified as a significant temporal cluster. This study assessed and mapped for the first time the spatiotemporal pattern of dengue fever in Nepal. Two districts namely Chitwan and Jhapa were found highly affected by dengue fever. The current study also demonstrated the importance of geospatial approach in epidemiological research. The initial result on dengue patterns and risk of this study may assist institutions and policy makers to develop better preventive strategies.

The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries.

PubMed

Aguiar, Maíra; Stollenwerk, Nico; Halstead, Scott B

2016-12-01

With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteur (CYD-TDV, named Dengvaxia), was able to protect, in the first 25 months of the two Phase III, 66% of a subset of 9-16 year old participants. However, a significantly lower efficacy (including negative vaccine efficacy) was noted for children younger than 9 years of age. Analysis of year 3 results of phase III trials of Dengvaxia suggest high rates of protection of vaccinated partial dengue immunes but high rates of hospitalizations during breakthrough dengue infections of persons who were vaccinated when seronegative, with vaccine appearing to induce enhancing antibodies (ADE). An age structured model was developed based on Sanofi's recommendation to vaccinate persons age 945 years in dengue endemic countries. The model was used to explore the clinical burden of two vaccination strategies: 1) Vaccinate 4 or 20% of individuals, ages 9-45 years, seropositives and seronegatives, and 2) vaccinate 4 or 20% of individuals, ages 9-45 years, who are dengue immune only. Our results show that vaccinating dengue monotypic immune individuals prevents dengue hospitalizations, but at the same time dengue infections of vaccine-sensitized persons increases hospitalizations. When the vaccine is given only to partial immune individuals, after immunological screening of the population, disease burden decreases considerably.

A case of dengue-related osteonecrosis of the maxillary dentoalveolar bone.

PubMed

Al-Namnam, N M; Nambiar, P; Shanmuhasuntharam, P; Harris, M

2017-06-01

Dengue is a mosquito transmitted flaviviral infection which can give rise to severe haemorrhage (dengue haemorrhagic fever) and with capillary leakage induces hypovolaemic shock (dengue shock syndrome). Although dengue symptoms and complications have been known for many decades, there has only been one documented case of osteonecrosis of the maxilla which was treated by excision of the necrotic bone. In this case of dengue infection, extensive maxillary osteonecrosis and minimal root resorption appeared to follow factitious injury with a toothpick but resolved with non-surgical management. © 2016 Australian Dental Association.

Self-reported pain intensity with the numeric reporting scale in adult dengue.

PubMed

Wong, Joshua G X; Gan, Victor C; Ng, Ee-Ling; Leo, Yee-Sin; Chan, Siew-Pang; Choo, Robin; Lye, David C

2014-01-01

Pain is a prominent feature of acute dengue as well as a clinical criterion in World Health Organization guidelines in diagnosing dengue. We conducted a prospective cohort study to compare levels of pain during acute dengue between different ethnicities and dengue severity. Demographic, clinical and laboratory data were collected. Data on self-reported pain was collected using the 11-point Numerical Rating Scale. Generalized structural equation models were built to predict progression to severe disease. A total of 499 laboratory confirmed dengue patients were recruited in the Prospective Adult Dengue Study at Tan Tock Seng Hospital, Singapore. We found no statistically significant differences between pain score with age, gender, ethnicity or the presence of co-morbidity. Pain score was not predictive of dengue severity but highly correlated to patients' day of illness. Prevalence of abdominal pain in our cohort was 19%. There was no difference in abdominal pain score between grades of dengue severity. Dengue is a painful disease. Patients suffer more pain at the earlier phase of illness. However, pain score cannot be used to predict a patient's progression to severe disease.

Current perspectives on dengue episode in Malaysia.

PubMed

Pang, Ee Leen; Loh, Hwei-San

2016-04-01

Prevalence of dengue transmission has been alarmed by an estimate of 390 million infections per annum. Urban encroachment, ecological disruption and poor sanitation are all contributory factors of increased epidemiology. Complication however arises from the fact that dengue virus inherently exists as four different serotypes. Secondary infection is often manifested in the more severe form, such that antibody-dependent enhancement (ADE) could aggravate ailment by allowing pre-existing antibodies to form complexes with infecting viruses as means of intrusion. Consequently, increased viraemic titter and suppression of antiviral response are observed. Deep concerns are thus expressed in regards to escalating trend of hospitalisation and mortality rates. In Malaysia, situation is exacerbated by improper clinical management and pending vector control operations. As a preparedness strategy against the potential deadly dengue pandemic, the call for development of a durable and cost-effective dengue vaccine against all infecting serotypes is intensified. Even though several vaccine candidates are currently being evaluated in clinical trials, uncertainties in regards to serotypes interference, incomplete protection and dose adequacy have been raised. Instead of sole reliance on outsourcing, production of local vaccine should be considered in coherent to government's efforts to combat against dengue. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Spatial patterns of dengue cases in Brazil

PubMed Central

Antonio, Fernando Jose; de Picoli, Sergio; Teixeira, Jorge Juarez Vieira; Mendes, Renio dos Santos

2017-01-01

Dengue infection plays a central role in our society, since it is the most prevalent vector-borne viral disease affecting humans. We statistically investigated patterns concerning the spatial spreading of dengue epidemics in Brazil, as well as their temporal evolution in all Brazilian municipalities for a period of 12 years. We showed that the distributions of cases in municipalities follow power laws persistent in time and that the infection scales linearly with the population of the municipalities. We also found that the average number of dengue cases does not have a clear dependence on the longitudinal position of municipalities. On the other hand, we found that the average distribution of cases varies with the latitudinal position of municipalities, displaying an almost constant growth from high latitudes until reaching the Tropic of Capricorn leveling to a plateau closer to the Equator. We also characterized the spatial correlation of the number of dengue cases between pairs of municipalities, where our results showed that the spatial correlation function decays with the increase of distance between municipalities, following a power-law with an exponential cut-off. This regime leads to a typical dengue traveling distance. Finally, we considered modeling this last behaviour within the framework of a Edwards-Wilkinson equation with a fractional derivative on space. PMID:28715435

Dengue among American missionaries returning from Jamaica, 2012.

PubMed

Moncayo, Abelardo C; Baumblatt, Jane; Thomas, Dana; Harvey, Kira A; Atrubin, David; Stanek, Danielle; Sotir, Mark; Hunsperger, Elizabeth; Muñoz-Jordan, Jorge L; Jentes, Emily S; Sharp, Tyler M; Arguello, D Fermin

2015-01-01

Dengue is an acute febrile illness caused by any of four mosquito-transmitted dengue virus (DENV) types. Dengue is endemic in Jamaica, where an epidemic occurred in 2012. An investigation was conducted by multiple agencies for 66 missionaries traveling from nine US states to Jamaica after 1 missionary from the group was confirmed to have dengue. Travelers were offered diagnostic testing, and a survey was administered to assess knowledge, behaviors, and illness. Of 42 survey respondents, 9 (21%) respondents reported an acute febrile illness during or after travel to Jamaica. Of 15 travelers that provided serum specimens, 4 (27%) travelers had detectable anti-DENV immunoglobulin M antibody, and 1 traveler also had DENV-1 detected by reverse transcriptase polymerase chain reaction. Recent or past infection with a DENV was evident in 93% (13 of 14) missionaries with available sera. No behavioral or demographic factors were significantly associated with DENV infection. This investigation shows that even trips of short duration to endemic areas present a risk of acquiring dengue. © The American Society of Tropical Medicine and Hygiene.

Co-occurrence Patterns of the Dengue Vector Aedes aegypti and Aedes mediovitattus, a Dengue Competent Mosquito in Puerto Rico

PubMed Central

Little, Eliza; Barrera, Roberto; Seto, Karen C.; Diuk-Wasser, Maria

2015-01-01

Aedes aegypti is implicated in dengue transmission in tropical and subtropical urban areas around the world. Ae. aegypti populations are controlled through integrative vector management. However, the efficacy of vector control may be undermined by the presence of alternative, competent species. In Puerto Rico, a native mosquito, Ae. mediovittatus, is a competent dengue vector in laboratory settings and spatially overlaps with Ae. aegypti. It has been proposed that Ae. mediovittatus may act as a dengue reservoir during inter-epidemic periods, perpetuating endemic dengue transmission in rural Puerto Rico. Dengue transmission dynamics may therefore be influenced by the spatial overlap of Ae. mediovittatus, Ae. aegypti, dengue viruses, and humans. We take a landscape epidemiology approach to examine the association between landscape composition and configuration and the distribution of each of these Aedes species and their co-occurrence. We used remotely sensed imagery from a newly launched satellite to map landscape features at very high spatial resolution. We found that the distribution of Ae. aegypti is positively predicted by urban density and by the number of tree patches, Ae. mediovittatus is positively predicted by the number of tree patches, but negatively predicted by large contiguous urban areas, and both species are predicted by urban density and the number of tree patches. This analysis provides evidence that landscape composition and configuration is a surrogate for mosquito community composition, and suggests that mapping landscape structure can be used to inform vector control efforts as well as to inform urban planning. PMID:21989642

Molecular surveillance of dengue in Minas Gerais provides insights on dengue virus 1 and 4 circulation in Brazil.

PubMed

Dutra, Karina Rocha; Drumond, Betânia Paiva; de Rezende, Izabela Maurício; Nogueira, Maurício Lacerda; de Oliveira Lopes, Débora; Calzavara Silva, Carlos Eduardo; Siqueira Ferreira, Jaqueline Maria; Dos Santos, Luciana Lara

2017-06-01

Dengue, caused by any of the four types of Dengue virus (DENV) is the most important arbovirus in the world. In this study we performed a molecular surveillance of dengue during the greatest dengue outbreak that took place in Divinópolis, Minas Gerais state, Southeast Brazil, in 2013. Samples from 100 patients with clinical symptoms of dengue were studied and 26 were positive. The capsid/premembrane (CprM) and envelope gene sequences of some samples were amplified and sequenced. Molecular analyses demonstrated that two DENV-1 lineages, belonging to genotype V were introduced and co-circulated in Divinópolis. When compared to each other, those lineages presented high genetic diversity and showed unique amino acids substitutions in the envelope protein, including in domains I, II, and III. DENV-4 strains from Divinópolis clustered within genotype IIb and the most recent common ancestor was probably introduced into the city three years before the 2013 epidemic. Here we demonstrated for the first time the circulation of DENV-4 and the co-circulation of two DENV-1 lineages in Midwest region of Minas Gerais, Brazil. Moreover our analysis indicated the introduction of five DENV-1 lineages, genotype V into Brazil, in different times. J. Med. Virol. 89:966-973, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Dengue fever: from disease to vaccination].

PubMed

Teyssou, R

2009-08-01

Dengue is a tropical disease affecting 110 countries throughout the world and placing over 3 billion people at risk of infection. According the World Health Organization 70 to 500 million persons are infected every year including 2 million who develop hemorrhagic form and 20,000 who die. Children are at highest risk for death. Due to the absence of specialized laboratories in most endemic regions and to the lack of specifici clinical presentation, the incidence of dengue and its economic costs are certainly underestimated. Dengue iscaused by an arbovirus belonging to the Flavivirus genus of the family Flaviviridae. There are four dengue virus serotypes and no cross protection between them. The disease is transmitted through the bites of mosquitoes belonging to the Aedes genus, mainly Aedes aegypti. However A. albopictus has played an important role in the spread of the disease and other species may be involved in specific locations (e.g., A. polynesiensis in the South Pacific). There is no specific treatment for dengue. Management of severe forms depends on symptomatic treatment of hemorrhagic complications and hypovolemic shock. Prevention requires control of vector mosquitoes that is difficult to implement and maintain. Dengue is a major emerging infectious disease with a heavy impact on public health. The high human and economic costs as well as the absence of specific preventive measures underscore the need to develop a vaccine. However finding and distributing such a vaccine to populations at risk is hampered by numerous obstacles. The most notable challenges standing in the way of development of a candidate vaccine are as follows: absence of an animal model, which has important implications for the preclinical development strategy; need to develop a live attenuated vaccine; existence of 4 antigenically distinct serotypes with the resulting risk of competition between vaccine strains; immunologic risks related to antibody-dependent enhancement that has been

Vaccination Against Dengue: Challenges and Current Developments.

PubMed

Guy, Bruno; Lang, Jean; Saville, Melanie; Jackson, Nicholas

2016-01-01

Dengue is a growing threat worldwide, and the development of a vaccine is a public health priority. The completion of the active phase of two pivotal efficacy studies conducted in Asia and Latin America by Sanofi Pasteur has constituted an important step. Several other approaches are under development, and whichever technology is used, vaccine developers face several challenges linked to the particular nature and etiology of dengue disease. We start our review by defining questions and potential issues linked to dengue pathology and presenting the main types of vaccine approaches that have explored these questions; some of these candidates are in a late stage of clinical development. In the second part of the review, we focus on the Sanofi Pasteur dengue vaccine candidate, describing the steps from research to phase III efficacy studies. Finally, we discuss what could be the next steps, before and after vaccine introduction, to ensure that the vaccine will provide the best benefit with an acceptable safety profile to the identified target populations.

Economic value of dengue vaccine in Thailand.

PubMed

Lee, Bruce Y; Connor, Diana L; Kitchen, Sarah B; Bacon, Kristina M; Shah, Mirat; Brown, Shawn T; Bailey, Rachel R; Laosiritaworn, Yongjua; Burke, Donald S; Cummings, Derek A T

2011-05-01

With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [< 1× per capita gross domestic product (GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [< 3× per capita GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving.

Economic Value of Dengue Vaccine in Thailand

PubMed Central

Lee, Bruce Y.; Connor, Diana L.; Kitchen, Sarah B.; Bacon, Kristina M.; Shah, Mirat; Brown, Shawn T.; Bailey, Rachel R.; Laosiritaworn, Yongjua; Burke, Donald S.; Cummings, Derek A. T.

2011-01-01

With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [< 1× per capita gross domestic product (GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [< 3× per capita GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving. PMID:21540387

Anti-GBM disease and ANCA during dengue infection.

PubMed

Lizarraga, Karlo J; Florindez, Jorge A; Daftarian, Pirouz; Andrews, David M; Ortega, Luis M; Mendoza, Jair Munoz; Contreras, Gabriel N; Nayer, Ali

2015-02-01

Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.

Treatment Effectiveness of Amantadine Against Dengue Virus Infection.

PubMed

Lin, Chieh-Cheng; Chen, Wen-Ching

2016-12-05

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

Meteorological factors affecting dengue incidence in Davao, Philippines.

PubMed

Iguchi, Jesavel A; Seposo, Xerxes T; Honda, Yasushi

2018-05-15

Dengue fever is a major public health concern in the Philippines, and has been a significant cause of hospitalizations and deaths among young children. Previous literature links climate change to dengue, and with increasingly unpredictable changing climate patterns, there is a need to understand how these meteorological variables affect dengue incidence in a highly endemic area. Weekly dengue incidences (2011-2015) in Davao Region, Philippines were obtained from the Department of Health. Same period of weekly local meteorological variables were obtained from the National Climatic Data Center (NCDC) and the National Oceanic and Atmospheric Administration (NOAA). Wavelet coherence analysis was used to determine the presence of non-stationary relationships, while a quasi-Poisson regression combined with distributed lag nonlinear model (DLNM) was used to analyze the association between meteorological variables and dengue incidences. Significant periodicity was detected in the 7 to 14-week band between the year 2011-2012 and a 26-week periodicity from the year 2013-2014. Overall cumulative risks were particularly high for rainfall at 32 mm (RR: 1.67, 95% CI: 1.07-2.62), while risks were observed to increase with increasing dew point. On the other hand, lower average temperature of 26 °C has resulted to an increased RR of dengue (RR: 1.96, 95% CI: 0.47-8.15) while higher temperature from 27 °C to 31 °C has lower RR. The observed possible threshold levels of these meteorological variables can be integrated into an early warning system to enhance dengue prediction for better vector control and management in the future.

Health Beliefs and Practices Related to Dengue Fever: A Focus Group Study

PubMed Central

Wong, Li Ping; AbuBakar, Sazaly

2013-01-01

Background This qualitative study aimed to provide an in-depth understanding of the meaning of dengue fever (DF) amongst people living in a dengue endemic region, dengue prevention and treatment-seeking behaviours. The Health Belief Model was used as a framework to explore and understand dengue prevention behaviours. Methods A total of 14 focus group discussions were conducted with 84 Malaysian citizens of different socio-demographic backgrounds between 16th December, 2011 and 12th May, 2012. Results The study revealed that awareness about DF and prevention measures were high. The pathophysiology of dengue especially dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) were rarely known; as a result, it was seen as deadly by some but was also perceived as easily curable by others without a basis of understanding. Young adults and elderly participants had a low perception of susceptibility to DF. In general, the low perceived susceptibility emerged as two themes, namely a perceived natural ability to withstand infection and a low risk of being in contact with the dengue virus vector, Aedes spp. mosquitoes. The barriers to sustained self-prevention against dengue prevention that emerged in focus groups were: i) lack of self-efficacy, ii) lack of perceived benefit, iii) low perceived susceptibility, and iv) unsure perceived susceptibility. Low perceived benefit of continued dengue prevention practices was a result of lack of concerted action against dengue in their neighborhood. Traditional medical practices and home remedies were widely perceived and experienced as efficacious in treating DF. Conclusion Behavioural change towards attaining sustainability in dengue preventive practices may be enhanced by fostering comprehensive knowledge of dengue and a change in health beliefs. Wide use of unconventional therapy for DF warrants the need to enlighten the public to limit their reliance on unproven alternative treatments. PMID:23875045

Community Willingness to Participate in a Dengue Study in Aceh Province, Indonesia

PubMed Central

Anwar, Samsul; Bustaman, Aslam; Radiansyah, Arsil; Angraini, Pradiba; Fasli, Riny; Salwiyadi, Salwiyadi; Bastian, Reza Akbar; Oktiviyari, Ade; Akmal, Imaduddin; Iqbalamin, Muhammad; Adil, Jamalul; Henrizal, Fenni; Darmayanti, Darmayanti; Pratama, Rovy; Fajar, Jonny Karunia; Setiawan, Abdul Malik; Imrie, Allison; Kuch, Ulrich; Groneberg, David Alexander; Sasmono, R. Tedjo; Dhimal, Meghnath; Müller, Ruth

2016-01-01

Background Dengue virus infection is the most rapidly spreading vector-borne disease in the world. Essential research on dengue virus transmission and its prevention requires community participation. Therefore, it is crucial to understand the factors that are associated with the willingness of communities in high prevalence areas to participate in dengue research. The aim of this study was to explore factors associated with the willingness of healthy community members in Aceh province, Indonesia, to participate in dengue research that would require phlebotomy. Methodology/Principal Findings A community-based cross-sectional study was carried out in nine regencies and municipalities of Aceh from November 2014 to March 2015. Interviews using a set of validated questionnaires were conducted to collect data on demography, history of dengue infection, socioeconomic status, and knowledge, attitude and practice regarding dengue fever. Two-step logistic regression and Spearman’s rank correlation (rs) analysis were used to assess the influence of independent variables on dependent variables. Among 535 participants, less than 20% had a good willingness to participate in the dengue study. The factors associated with good willingness to participate were being female, working as a civil servant, private employee or entrepreneur, having a high socioeconomic status and good knowledge, attitude and practice regarding dengue. Good knowledge and attitude regarding dengue were positive independent predictors of willingness to participate (OR: 2.30 [95% CI: 1.36–3.90] and 3.73 [95% CI: 2.24–6.21], respectively). Conclusion/Significance The willingness to participate in dengue research is very low among community members in Aceh, and the two most important associated factors are knowledge and attitude regarding dengue. To increase participation rate, efforts to improve the knowledge and attitude of community members regarding dengue fever and dengue-related research is required

Health beliefs and practices related to dengue fever: a focus group study.

PubMed

Wong, Li Ping; AbuBakar, Sazaly

2013-01-01

This qualitative study aimed to provide an in-depth understanding of the meaning of dengue fever (DF) amongst people living in a dengue endemic region, dengue prevention and treatment-seeking behaviours. The Health Belief Model was used as a framework to explore and understand dengue prevention behaviours. A total of 14 focus group discussions were conducted with 84 Malaysian citizens of different socio-demographic backgrounds between 16(th) December, 2011 and 12(th) May, 2012. The study revealed that awareness about DF and prevention measures were high. The pathophysiology of dengue especially dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) were rarely known; as a result, it was seen as deadly by some but was also perceived as easily curable by others without a basis of understanding. Young adults and elderly participants had a low perception of susceptibility to DF. In general, the low perceived susceptibility emerged as two themes, namely a perceived natural ability to withstand infection and a low risk of being in contact with the dengue virus vector, Aedes spp. mosquitoes. The barriers to sustained self-prevention against dengue prevention that emerged in focus groups were: i) lack of self-efficacy, ii) lack of perceived benefit, iii) low perceived susceptibility, and iv) unsure perceived susceptibility. Low perceived benefit of continued dengue prevention practices was a result of lack of concerted action against dengue in their neighborhood. Traditional medical practices and home remedies were widely perceived and experienced as efficacious in treating DF. Behavioural change towards attaining sustainability in dengue preventive practices may be enhanced by fostering comprehensive knowledge of dengue and a change in health beliefs. Wide use of unconventional therapy for DF warrants the need to enlighten the public to limit their reliance on unproven alternative treatments.

Classical dengue hemorrhagic fever resulting from two dengue infections spaced 20 years or more apart: Havana, Dengue 3 epidemic, 2001-2002.

PubMed

González, Daniel; Castro, Osvaldo E; Kourí, Gustavo; Perez, Jorge; Martinez, Eric; Vazquez, Susana; Rosario, Delfina; Cancio, Reynel; Guzman, María G

2005-09-01

To report the clinical, laboratory and sonographic findings in 76 adult cases of dengue hemorrhagic fever (DHF). A dengue 3 epidemic occurred in Havana City from June 2001 to March 2002. 12,889 cases were reported, with 81 DHF cases. From this, 76 serologically confirmed cases were studied descriptively. Bronchial asthma and white race were important risk factors for the severe form of the disease. Fever (100%), headache (92.1%), myalgia (76.3%), arthralgia (73.7%) and retro-orbital pain (57.7%) were the most frequent general symptoms. Vomiting and abdominal pain were observed in 59.2% and 48.6% of cases, respectively. The most common bleeding site was the vagina (64%), followed by the skin (55.2%). Eighteen patients (23.6%) had shock syndrome. Laboratory findings included thrombocytopenia (100%), hemoconcentration (93.4%), an increase in liver enzymes (82.8%), and leukopenia (71%). Ultrasound detected thickening of the gallbladder wall in 35.1%, pleural effusion in 20.3%, and splenomegaly in 12.9% of cases. These findings contribute to a better understanding of the clinical aspects of DHF in adult patients due to the dengue 3 virus.

A tetravalent dengue nanoparticle stimulates antibody production in mice.

PubMed

Silva, Elisângela F; Orsi, Mariana; Andrade, Angela L; Domingues, Rosana Z; Silva, Breno M; de Araújo, Helena R C; Pimenta, Paulo F P; Diamond, Michael S; Rocha, Eliseu S O; Kroon, Erna G; Malaquias, Luiz C C; Coelho, Luiz F L

2012-03-22

Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines. Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested. Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.

Dengue Virus Exposures Among Deployed U.S. Military Personnel

PubMed Central

Hesse, Elisabeth M.; Martinez, Luis J.; Jarman, Richard G.; Lyons, Arthur G.; Eckels, Kenneth H.; De La Barrera, Rafael A.; Thomas, Stephen J.

2017-01-01

Dengue virus infections have adversely impacted U.S. military operations since the Spanish–American War. The erosion of mission capabilities and lost duty days are underestimated. Appreciating the incidence and prevalence of dengue infections in U.S. military personnel is important to inform disease prevention strategies. Banked pre- and post-deployment serum samples from 1,000 U.S. military personnel with a single deployment to a dengue-endemic region were tested using a screening microneutralization assay to detect anti-dengue-virus-neutralizing antibodies. A total of 76 (7.6%) post-deployment samples were positive and 15 of the pre-deployment samples were negative. These figures represent an infection incidence of 1.5% and total of 17.6 seroconversions per 10,000 deployment months. These data represent a deploying military population with a relatively high background rate of dengue seropositivity, a low level of infection during deployment compared with background infection rates in the local populations, and the potential for worsening clinical attack rates with increased frequency of deployment. Additional studies are required to more clearly elucidate the dengue infection and disease risk in U.S. military personnel. PMID:28193746

Dengue Virus Exposures Among Deployed U.S. Military Personnel.

PubMed

Hesse, Elisabeth M; Martinez, Luis J; Jarman, Richard G; Lyons, Arthur G; Eckels, Kenneth H; De La Barrera, Rafael A; Thomas, Stephen J

2017-05-01

AbstractDengue virus infections have adversely impacted U.S. military operations since the Spanish-American War. The erosion of mission capabilities and lost duty days are underestimated. Appreciating the incidence and prevalence of dengue infections in U.S. military personnel is important to inform disease prevention strategies. Banked pre- and post-deployment serum samples from 1,000 U.S. military personnel with a single deployment to a dengue-endemic region were tested using a screening microneutralization assay to detect anti-dengue-virus-neutralizing antibodies. A total of 76 (7.6%) post-deployment samples were positive and 15 of the pre-deployment samples were negative. These figures represent an infection incidence of 1.5% and total of 17.6 seroconversions per 10,000 deployment months. These data represent a deploying military population with a relatively high background rate of dengue seropositivity, a low level of infection during deployment compared with background infection rates in the local populations, and the potential for worsening clinical attack rates with increased frequency of deployment. Additional studies are required to more clearly elucidate the dengue infection and disease risk in U.S. military personnel.

Clinical and laboratory factors associated with mortality in dengue.

PubMed

Saroch, Atul; Arya, Vivek; Sinha, Nitin; Taneja, R S; Sahai, Pooja; Mahajan, R K

2017-04-01

Dengue is endemic in more than 100 countries, giving rise to an increased number of deaths in the last five years in the South-East Asian region. We report our findings from a retrospective study of adults admitted with confirmed dengue at our institution. We studied the clinical and laboratory parameters associated with mortality in these patients. Of the 172 hospitalised patients studied, 156 (90.69 %) recovered while 16 (9.3%) died. Univariate analysis showed altered sensorium on presentation, lower haemoglobin and haematocrit levels, higher serum creatinine, higher serum transaminase and lower serum albumin levels to be significantly associated with mortality in dengue. Further, using stepwise multivariate logistic regression, altered sensorium ( P = 0.006) and hypoalbuminemia ( P = 0.013) were identified as independent predictors of mortality in dengue. Identification of these parameters early in the course of disease should prompt intensification of treatment in dengue cases.

Can internet search queries be used for dengue fever surveillance in China?

PubMed

Guo, Pi; Wang, Li; Zhang, Yanhong; Luo, Ganfeng; Zhang, Yanting; Deng, Changyu; Zhang, Qin; Zhang, Qingying

2017-10-01

China experienced an unprecedented outbreak of dengue fever in 2014, and the number of cases reached the highest level over the past 25 years. Traditional sentinel surveillance systems of dengue fever in China have an obvious drawback that the average delay from receipt to dissemination of dengue case data is roughly 1-2 weeks. In order to exploit internet search queries to timely monitor dengue fever, we analyzed data of dengue incidence and Baidu search query from 31 provinces in mainland China during the period of January 2011 to December 2014. We found that there was a strong correlation between changes in people's online health-seeking behavior and dengue fever incidence. Our study represents the first attempt demonstrating a strong temporal and spatial correlation between internet search trends and dengue epidemics nationwide in China. The findings will help the government to strengthen the capacity of traditional surveillance systems for dengue fever. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Dengue hemorrhagic fever and acute hepatitis: a case report.

PubMed

Mourão, Maria Paula Gomes; Lacerda, Marcus Vinícius Guimarães de; Bastos, Michele de Souza; Albuquerque, Bernardino Cláudio de; Alecrim, Wilson Duarte

2004-12-01

Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

Dengue-associated hemophagocytic syndrome in a Japanese traveler: a case report.

PubMed

Kobayashi, Ken-ichiro; Hikone, Mayu; Sakamoto, Naoya; Iwabuchi, Sentaro; Kashiura, Masahiro; Takasaki, Tomohiko; Fujita, Hiroshi; Ohnishi, Kenji

2015-01-01

Hemophagocytic syndrome (HPS) can develop as a complication of dengue in rare cases, but its relationship with dengue is not well known. We report a case of dengue-associated HPS with liver involvement and coagulopathy. The patient, a Japanese female traveler who had recently returned from Thailand, had severe complications of dengue infection, but she recovered fully with symptomatic treatment. © 2014 International Society of Travel Medicine.

The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries

PubMed Central

Stollenwerk, Nico; Halstead, Scott B.

2016-01-01

Background With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteur (CYD-TDV, named Dengvaxia), was able to protect, in the first 25 months of the two Phase III, 66% of a subset of 9–16 year old participants. However, a significantly lower efficacy (including negative vaccine efficacy) was noted for children younger than 9 years of age. Methodology/Principal Findings Analysis of year 3 results of phase III trials of Dengvaxia suggest high rates of protection of vaccinated partial dengue immunes but high rates of hospitalizations during breakthrough dengue infections of persons who were vaccinated when seronegative, with vaccine appearing to induce enhancing antibodies (ADE). An age structured model was developed based on Sanofi’s recommendation to vaccinate persons age 945 years in dengue endemic countries. The model was used to explore the clinical burden of two vaccination strategies: 1) Vaccinate 4 or 20% of individuals, ages 9–45 years, seropositives and seronegatives, and 2) vaccinate 4 or 20% of individuals, ages 9–45 years, who are dengue immune only. Conclusions/Significance Our results show that vaccinating dengue monotypic immune individuals prevents dengue hospitalizations, but at the same time dengue infections of vaccine-sensitized persons increases hospitalizations. When the vaccine is given only to partial immune individuals, after immunological screening of the population, disease burden decreases considerably. PMID:28002420

The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue

PubMed Central

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

2016-01-01

Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt

The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue.

PubMed

Ng, Deborah Hl; Wong, Joshua Gx; Thein, Tun-Linn; Leo, Yee-Sin; Lye, David C

2016-01-01

Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR) confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration) was present in 572 (20.1%) of patients. Dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and severe dengue (SD) were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT) and aspartate transaminase (AST), higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT) were significantly associated with prolonged fever but not platelet count or prothrombin time (PT). Saddleback fever was present in 165 (5.8%). Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF), while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore prompt

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.

Dengue Vectors and their Spatial Distribution

PubMed Central

Higa, Yukiko

2011-01-01

The distribution of dengue vectors, Ae. aegypti and Ae. albopictus, is affected by climatic factors. In addition, since their life cycles are well adapted to the human environment, environmental changes resulting from human activity such as urbanization exert a great impact on vector distribution. The different responses of Ae. aegypti and Ae albopictus to various environments result in a difference in spatial distribution along north-south and urban-rural gradients, and between the indoors and outdoors. In the north-south gradient, climate associated with survival is an important factor in spatial distribution. In the urban-rural gradient, different distribution reflects a difference in adult niches and is modified by geographic and human factors. The direct response of the two species to the environment around houses is related to different spatial distribution indoors and outdoors. Dengue viruses circulate mainly between human and vector mosquitoes, and the vector presence is a limiting factor of transmission. Therefore, spatial distribution of dengue vectors is a significant concern in the epidemiology of the disease. Current technologies such as GIS, satellite imagery and statistical models allow researchers to predict the spatial distribution of vectors in the changing environment. Although it is difficult to confirm the actual effect of environmental and climate changes on vector abundance and vector-borne diseases, environmental changes caused by humans and human behavioral changes due to climate change can be expected to exert an impact on dengue vectors. Longitudinal monitoring of dengue vectors and viruses is therefore necessary. PMID:22500133

Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection.

PubMed

Cui, Liang; Hou, Jue; Fang, Jinling; Lee, Yie Hou; Costa, Vivian Vasconcelos; Wong, Lan Hiong; Chen, Qingfeng; Ooi, Eng Eong; Tannenbaum, Steven R; Chen, Jianzhu; Ong, Choon Nam

2017-07-15

Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend-most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. IMPORTANCE Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly

Household costs of hospitalized dengue illness in semi-rural Thailand

PubMed Central

Ratanawong, Pitcha; Sewe, Maquines Odhiambo; Wilder-Smith, Annelies; Kittayapong, Pattamaporn

2017-01-01

Background Dengue-related illness is a leading cause of hospitalization and death in Thailand and other Southeast Asian countries, imposing a major economic burden on households, health systems, and governments. This study aims to assess the economic impact of hospitalized dengue cases on households in Chachoengsao province in eastern Thailand. Methods We conducted a prospective cost-of-illness study of hospitalized pediatric and adult dengue patients at three public hospitals. We examined all hospitalized dengue cases regardless of disease severity. Patients or their legal guardians were interviewed using a standard questionnaire to determine household-level medical and non-medical expenditures and income losses during the illness episode. Results Between March and September 2015, we recruited a total of 224 hospitalized patients (<5 years, 4%; 5–14 years, 20%, 15–24 years, 36%, 25–34 years, 15%; 35–44 years, 10%; 45+ years, 12%), who were clinically diagnosed with dengue. The total cost of a hospitalized dengue case was higher for adult patients than pediatric patients, and was US$153.6 and US$166.3 for pediatric DF and DHF patients, respectively, and US$171.2 and US$226.1 for adult DF and DHF patients, respectively. The financial burden on households increased with the severity of dengue illness. Conclusions Although 74% of the households reported that the patient received free medical care, hospitalized dengue illness cost approximately 19–23% of the monthly household income. These results indicated that dengue imposed a substantial financial burden on households in Thailand where a great majority of the population was covered by the Universal Coverage Scheme for health care. PMID:28937986

Understanding dengue pathogenesis: implications for vaccine design.

PubMed Central

Stephenson, John R.

2005-01-01

In the second half of the twentieth century dengue spread throughout the tropics, threatening the health of a third of the world's population. Dengue viruses cause 50-100 million cases of acute febrile disease every year, including more than 500,000 reported cases of the severe forms of the disease--dengue haemorrhagic fever and dengue shock syndrome. Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. The current understanding of dengue pathogenesis is outlined in this review, with special emphasis on the role of the immune response. The suspected involvement of the immune system in increased disease severity and vascular damage has raised concerns about every vaccine design strategy proposed so far. Clearly more research is needed on understanding the correlates of protection and mechanisms of pathogenesis. There is, however, an urgent need to provide a solution to the escalating global public health problems caused by dengue infections. Better disease management, vector control and improved public health measures will help reduce the current disease burden, but a safe and effective vaccine is probably the only long-term solution. Although concerns have been raised about the possible safety and efficacy of both conventional and novel vaccine technologies, the situation is now so acute that it is not possible to wait for the perfect vaccine. Consequently the careful and thorough evaluation of several of the current candidate vaccines may be the best approach to halting the spread of disease. PMID:15868023

Self-Reported Pain Intensity with the Numeric Reporting Scale in Adult Dengue

PubMed Central

Wong, Joshua G. X.; Gan, Victor C.; Ng, Ee-Ling; Leo, Yee-Sin; Chan, Siew-Pang; Choo, Robin; Lye, David C.

2014-01-01

Background Pain is a prominent feature of acute dengue as well as a clinical criterion in World Health Organization guidelines in diagnosing dengue. We conducted a prospective cohort study to compare levels of pain during acute dengue between different ethnicities and dengue severity. Methods Demographic, clinical and laboratory data were collected. Data on self-reported pain was collected using the 11-point Numerical Rating Scale. Generalized structural equation models were built to predict progression to severe disease. Results A total of 499 laboratory confirmed dengue patients were recruited in the Prospective Adult Dengue Study at Tan Tock Seng Hospital, Singapore. We found no statistically significant differences between pain score with age, gender, ethnicity or the presence of co-morbidity. Pain score was not predictive of dengue severity but highly correlated to patients’ day of illness. Prevalence of abdominal pain in our cohort was 19%. There was no difference in abdominal pain score between grades of dengue severity. Conclusion Dengue is a painful disease. Patients suffer more pain at the earlier phase of illness. However, pain score cannot be used to predict a patient’s progression to severe disease. PMID:24788828

Sensorineural hearing loss in hemorrhagic dengue?

PubMed

Ribeiro, Bruna Natália Freire; Guimarães, Alexandre Caixeta; Yazawa, Felipe; Takara, Tammy Fumiko Messias; de Carvalho, Guilherme Machado; Zappelini, Carlos Eduardo Monteiro

2015-01-01

Dengue is an acute febrile infectious disease, with high fever followed by symptoms flu-like. Dengue hemorrhagic fever (DHF) is a vascular leak syndrome and could present spontaneous bleeding and worsening of symptoms after some days. Dengue could have some ENT manifestations, however hearing loss is not one of them. Sudden hearing loss is considered as sensorineural or perceptual hearing loss with a sudden onset in a person without other prior otological history. The relation between infectious diseases and sudden hearing are been investigated, some viruses were already linked, but the relation between dengue virus and sudden hearing still remains unknown. This article has the goal of presenting a case of DHF that evolved with SSHL in his hospitalization process. We report a 60 years-male patient of with DHF who developed bilateral secretory otitis media and sensorineural hearing loss after the fifth day of onset of symptoms. His hearing loss remained even after 7 months and the patient was referred for hearing aid fitting. This is the first case report that brings together DHF and sudden hearing loss. In the development of this case no other cause to sudden hearing loss was found and the correlation between dengue and hearing loss was questioned. In the literature review was found that some viruses, as mumps virus, varicella-zoster virus and HSV-1 and HSV-2 are related to sudden hearing loss, all of them fit in the viral theory. Besides the viral theory of sudden hearing loss, there is the vascular theory that is the occlusion of the end artery that supplies the cochlea. DHF has a vascular commitment, and the hypothesis of a vascular cause could be elicited in this case. Many studies in this area are needed and this article has the objective of elicit the discussion about the subject. Could dengue be associated with sensorineural hearing loss? Copyright © 2015. Published by Elsevier Ltd.

Clinical and virological characteristics of dengue in Surabaya, Indonesia.

PubMed

Wardhani, Puspa; Aryati, Aryati; Yohan, Benediktus; Trimarsanto, Hidayat; Setianingsih, Tri Y; Puspitasari, Dwiyanti; Arfijanto, Muhammad Vitanata; Bramantono, Bramantono; Suharto, Suharto; Sasmono, R Tedjo

2017-01-01

Dengue disease is still a major health problem in Indonesia. Surabaya, the second largest city in the country, is endemic for dengue. We report here on dengue disease in Surabaya, investigating the clinical manifestations, the distribution of dengue virus (DENV) serotypes, and the relationships between clinical manifestations and the genetic characteristics of DENV. A total of 148 patients suspected of having dengue were recruited during February-August 2012. One hundred one (68%) of them were children, and 47 (32%) were adults. Dengue fever (DF) and Dengue hemorrhagic fever (DHF) were equally manifested in all of the patients. We performed DENV serotyping on all of the samples using real-time RT-PCR. Of 148, 79 (53%) samples were detected as DENV positive, with DENV-1 as the predominant serotype (73%), followed by DENV-2 (8%), DENV-4 (8%), and DENV-3 (6%), while 5% were mixed infections. Based on the Envelope gene sequences, we performed phylogenetic analyses of 24 isolates to genotype the DENV circulating in Surabaya in 2012, and the analysis revealed that DENV-1 consisted of Genotypes I and IV, DENV-2 was of the Cosmopolitan genotype, the DENV-3 viruses were of Genotype I, and DENV-4 was detected as Genotype II. We correlated the infecting DENV serotypes with clinical manifestations and laboratory parameters; however, no significant correlations were found. Amino acid analysis of Envelope protein did not find any unique mutations related to disease severity.

Clinical and virological characteristics of dengue in Surabaya, Indonesia

PubMed Central

Wardhani, Puspa; Aryati, Aryati; Yohan, Benediktus; Trimarsanto, Hidayat; Setianingsih, Tri Y.; Puspitasari, Dwiyanti; Arfijanto, Muhammad Vitanata; Bramantono, Bramantono; Suharto, Suharto

2017-01-01

Dengue disease is still a major health problem in Indonesia. Surabaya, the second largest city in the country, is endemic for dengue. We report here on dengue disease in Surabaya, investigating the clinical manifestations, the distribution of dengue virus (DENV) serotypes, and the relationships between clinical manifestations and the genetic characteristics of DENV. A total of 148 patients suspected of having dengue were recruited during February-August 2012. One hundred one (68%) of them were children, and 47 (32%) were adults. Dengue fever (DF) and Dengue hemorrhagic fever (DHF) were equally manifested in all of the patients. We performed DENV serotyping on all of the samples using real-time RT-PCR. Of 148, 79 (53%) samples were detected as DENV positive, with DENV-1 as the predominant serotype (73%), followed by DENV-2 (8%), DENV-4 (8%), and DENV-3 (6%), while 5% were mixed infections. Based on the Envelope gene sequences, we performed phylogenetic analyses of 24 isolates to genotype the DENV circulating in Surabaya in 2012, and the analysis revealed that DENV-1 consisted of Genotypes I and IV, DENV-2 was of the Cosmopolitan genotype, the DENV-3 viruses were of Genotype I, and DENV-4 was detected as Genotype II. We correlated the infecting DENV serotypes with clinical manifestations and laboratory parameters; however, no significant correlations were found. Amino acid analysis of Envelope protein did not find any unique mutations related to disease severity. PMID:28575000

Fulminant hepatic failure in an infant with severe dengue infection.

PubMed

Soundravally, R; Narayanan, P; Bhat, B Vishnu; Soundraragavan, Jayanthi; Setia, Sajita

2010-04-01

Fulminant hepatic failure due to dengue infection is rare, although mild liver dysfunction is common. Here we report a fatal case of fulminant hepatitis in an infant infected with dengue 3 serotype. Attention must be given to the use of hepatotoxic drugs in some cases of dengue especially in infants.

Dengue data and surveillance in Tanzania: a systematic literature review.

PubMed

Ward, Tara; Samuel, Moody; Maoz, Dorit; Runge-Ranzinger, Silvia; Boyce, Ross; Toledo, Joao; Velayudhan, Raman; Horstick, Olaf

2017-08-01

Although there is evidence that dengue virus is circulating in Tanzania, the country lacks a dengue surveillance system. Consequently, the true estimate of dengue seroprevalence, as well as the incidence in the population, the frequency and magnitude of outbreaks is unknown. This study therefore sought to systematically review available dengue data from Tanzania. The systematic review was conducted and reported using the PRISMA tool. Five databases (PubMed, Embase, Web of Science, WHOLIS and Google Scholar) were searched for articles using various keywords on the illness, data and geographical location. Identified articles were assessed for inclusion based on predefined eligibility criteria. Data were extracted from included articles, analysed and reported. Based on the 10 seroprevalence studies in defined populations with estimates of acute confirmed infections that were included in the review, the estimated seroprevalence of past dengue infection in Tanzania ranged from 50.6% in a health facility-based study to 11% in a population-based study. Acute confirmed infections of dengue were estimated to be as high as 38.2% of suspected cases. Only one study reported on an outbreak. It is evident that dengue needs to become part of regular disease surveillance in Tanzania. Control measures need to be instituted with a focus on building human resource capacity and integrating dengue control measures in ongoing health programmes, for both preventive and curative interventions. Systematic reviews are valuable in assessing health issues when surveillance data are not available. © 2017 John Wiley & Sons Ltd.

Economic and Disease Burden of Dengue Illness in India

PubMed Central

Shepard, Donald S.; Halasa, Yara A.; Tyagi, Brij Kishore; Adhish, S. Vivek; Nandan, Deoki; Karthiga, K. S.; Chellaswamy, Vidya; Gaba, Mukul; Arora, Narendra K.

2014-01-01

Between 2006 and 2012 India reported an annual average of 20,474 dengue cases. Although dengue has been notifiable since 1996, regional comparisons suggest that reported numbers substantially underrepresent the full impact of the disease. Adjustment for underreporting from a case study in Madurai district and an expert Delphi panel yielded an annual average of 5,778,406 clinically diagnosed dengue cases between 2006 and 2012, or 282 times the reported number per year. The total direct annual medical cost was US$548 million. Ambulatory settings treated 67% of cases representing 18% of costs, whereas 33% of cases were hospitalized, comprising 82% of costs. Eighty percent of expenditures went to private facilities. Including non-medical and indirect costs based on other dengue-endemic countries raises the economic cost to $1.11 billion, or $0.88 per capita. The economic and disease burden of dengue in India is substantially more than captured by officially reported cases, and increased control measures merit serious consideration. PMID:25294616

Dengue Risk among Visitors to Hawaii during an Outbreak

PubMed Central

Smith, Carrie E.; Tom, Tammy; Sasaki, Jed; Ayers, Tracy

2005-01-01

Despite the high rates of dengue in many tropical destinations frequented by tourists, limited information is available on the risk for infection among short-term visitors. We retrospectively surveyed 4,000 persons who arrived in Hawaii during the peak of the 2001–2002 dengue outbreak and collected follow-up serologic test results for those reporting denguelike illness. Of 3,064 visitors who responded, 94 (3%) experienced a denguelike illness either during their trip or within 14 days of departure; 34 of these persons were seen by a physician, and 2 were hospitalized. Twenty-seven visitors with denguelike illness provided a serum specimen; all specimens were negative for anti-dengue immunoglobulin G antibodies. The point estimate of dengue incidence was zero infections per 358 person-days of exposure with an upper 95% confidence limit of 3.0 cases per person-year. Thus, the risk for dengue infection for visitors to Hawaii during the outbreak was low. PMID:15890133

Reappearance of chikungunya, formerly called dengue, in the Americas.

PubMed

Halstead, Scott B

2015-04-01

After an absence of ≈200 years, chikungunya returned to the American tropics in 2013. The virus is maintained in a complex African zoonotic cycle but escapes into an urban cycle at 40- to 50-year intervals, causing global pandemics. In 1823, classical chikungunya, a viral exanthem in humans, occurred on Zanzibar, and in 1827, it arrived in the Caribbean and spread to North and South America. In Zanzibar, the disease was known as kidenga pepo, Swahili for a sudden cramp-like seizure caused by an evil spirit; in Cuba, it was known as dengue, a Spanish homonym of denga. During the eighteenth century, dengue (present-day chikungunya) was distinguished from breakbone fever (present-day dengue), another febrile exanthem. In the twentieth century, experiments resulted in the recovery and naming of present-day dengue viruses. In 1952, chikungunya virus was recovered during an outbreak in Tanzania, but by then, the virus had lost its original name to present-day dengue viruses.

Quality of Life among Adults with Confirmed Dengue in Brazil

PubMed Central

Martelli, Celina Maria Turchi; Nascimento, Nazareth Elias; Suaya, Jose A.; Siqueira, Joao Bosco; Souza, Wayner Vieira; Turchi, Marilia Dalva; Guilarde, Adriana Oliveira; Peres, Joao Borges; Shepard, Donald S.

2011-01-01

The main objective of this study was to measure the quality of life (QoL) during a dengue episode. We conducted a facility-based survey in central Brazil in 2005 and recruited 372 laboratory-confirmed dengue patients greater than 12 years of age in hospital and ambulatory settings. We administered the World Health Organization QoL instrument approximately 15 days after the onset of symptoms. We used principal component analysis with varimax rotation to identify domains related to QoL. The median age of interviewees was 36 years. Most (85%) reported their general health status as very good or good before the dengue episode. Although ambulatory patients were mainly classified as having dengue fever, 44.8% of hospitalized patients had dengue hemorrhagic fever or intermediate dengue. Principal component analysis identified five principal components related to cognition, sleep and energy, mobility, self-care, pain, and discomfort, which explained 73% of the variability of the data matrix. Hospitalized patients had significantly lower mean scores for dimensions cognition, self-care, and pain than ambulatory patients. This investigation documented the generally poor QoL during a dengue episode caused by the large number of domains affected and significant differences between health care settings. PMID:21976580

Serological Evidence of Dengue Fever Among Refugees, Hargeysa, Somalia

DTIC Science & Technology

1989-01-01

fever, Sindbis, Chikungunya, yellow HISTORY OF THE DISEASE IN THE fever, and Zika viruses . However, antibody reac- DAM CAMP tive to dengue 2 virus was...fever, Crimean-Congo hemorrhagic fever, Sindbis, Chikungunya, yellow fever, and Zika viruses . However, antibody reactive to dengue 2 virus was detected... ZIKA ) viruses . Further testing of sera for evidence of dengue S Barbera S , MOGAISCIO . viral infection was done by the enzyme immunoassay " (EIA

Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever

PubMed Central

Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R.

2016-01-01

Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism–serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved

A rare case of dengue encephalopathy complicating a term pregnancy.

PubMed

Rajagopala, Lavanya; Satharasinghe, Ravindra L; Karunarathna, Madhava

2017-02-02

Dengue fever has an expanded clinical spectrum ranging from an asymptomatic infection to life threatening dengue hemorrhagic fever and refractory shock. Dengue infection in pregnancy can be a diagnostic dilemma, particularly considering the physiological changes in pregnancy and the obstetric complications encountered in clinical practice. Hence the knowledge of its diagnosis and management in its atypical presentations is of paramount importance. Here we report an unusual case of uncomplicated dengue encephalopathy in a term mother, probably the first to be reported from the Indian subcontinent. A 28 year old woman, 37 weeks of pregnancy presented with fever of four days duration. She eventually developed irritability, altered sensorium, somnolence, and unresponsiveness to commands by the 5th day of febrile illness without any circulatory compromise. Physical examination and investigations including serology confirmed dengue fever. After excluding all other possible causes, the transient neurological deterioration was finally attributed to dengue encephalopathy which is an uncommon manifestation of the disease, particularly in pregnancy. Her deteriorated neurological status which had lasted for 6 days improved spontaneously with the convalescence of dengue infection. Cautious fluid management was carried out in correlation to clinical and hematological parameters. The pregnancy was continued uncomplicated till the platelet count had risen to more than 50,000 cells/cumm. She delivered vaginally a healthy male baby. Dengue fever in pregnancy is increasingly being encountered due to its rising disease burden. Dengue encephalitis/encephalopathy must be suspected in the differential diagnosis of fever and altered sensorium, even in pregnancy, in the tropical countries where the infection is rampant. Management of dengue infection in term pregnancy is a challenge for both the clinician and obstetrician. Further discussion and research are mandatory to decide on

Estimating the Risk of Vertical Transmission of Dengue: A Prospective Study.

PubMed

Basurko, Célia; Matheus, Séverine; Hildéral, Hélène; Everhard, Sibille; Restrepo, Marion; Cuadro-Alvarez, Emma; Lambert, Véronique; Boukhari, Rachida; Duvernois, Jean-Pierre; Favre, Anne; Nacher, Mathieu; Carles, Gabriel

2018-04-23

The incidence of dengue worldwide is increasing rapidly. A better understanding of dengue transmission may help improve interventions against this major public health problem. The virus is mostly transmitted by vectors. There are, however, other modes of transmission, notably mother-to-child transmission or vertical transmission. We studied a prospective cohort of 54 women who had dengue while pregnant during the 2012-2013 epidemic in French Guiana to estimate the mother-to-child transmission rate and assess the clinical and biological presentation of neonatal dengue. The rate of vertical transmission was between 18.5% (95% confidence interval [CI]: 9.25-31.4) and 22.7% (95% CI: 11.5-37.8), depending on the calculation method used. Mother-to-child transmission occurred both in early and late pregnancy. There were 52 births, including three newborns who presented neonatal dengue with warning signs requiring platelet transfusion. This quantification of the mother-to-child transmission of dengue highlights three points: first, vertical transmission of dengue is not negligible; second, it is more frequent when maternal dengue occurs late during pregnancy near delivery; and third, reliable diagnostic tests must be used to allow the diagnosis of vertical transmission. Our findings indicate that if there is a known history of maternal dengue during pregnancy, or if there is fever during the 15 days before term, cord blood and placenta should be sampled after delivery and tested for the virus, and the newborn should be closely monitored during the postpartum period.

Preventing dengue and chikungunya fever among international travelers.

PubMed

Tither, Pauline Herold

2014-11-01

To describe the vulnerability of U.S. travelers in tropical and subtropical regions of the world to dengue and chikungunya fever, to provide practical recommendations to avoid these mosquito-borne diseases, and to offer a communication tool as an aid for pretravel health consultations. Medical, epidemiological, and entomological research articles and reviews, and reports from government agencies. Dengue and chikungunya fever have growing public health impact around the world. International travelers return to the United States infected with these diseases. Mosquito bite avoidance is the only way to prevent dengue and chikungunya fever. Informed travelers have many options for simple and practical measures to lessen the risk of mosquito bites. A message map can be used as a communication tool for pretravel counseling on the prevention of dengue and chikungunya fever within the time frame of an office visit. In a pretravel health consultation, a nurse practitioner can promote travelers' health and prevent dengue, chikungunya fever, and other mosquito-borne diseases by counseling on the risk of these diseases and giving practical recommendations for prevention using a message map. ©2014 American Association of Nurse Practitioners.

Isolation and characterization of dengue virus serotype 2 from the large dengue outbreak in Guangdong, China in 2014.

PubMed

Zhao, Hui; Zhao, LingZhai; Jiang, Tao; Li, XiaoFeng; Fan, Hang; Hong, WenXin; Zhang, Yu; Zhu, Qin; Ye, Qing; Tong, YiGang; Cao, WuChun; Zhang, FuChun; Qin, ChengFeng

2014-12-01

Dengue has been well recognized as a global public health threat, but only sporadic epidemics and imported cases were reported in recent decades in China. Since July 2014, an unexpected large dengue outbreak has occurred in Guangdong province, China, resulting in more than 40000 patients including six deaths. To clarify and characterize the causative agent of this outbreak, the acute phase serum from a patient diagnosed with severe dengue was subjected to virus isolation and high-throughput sequencing (HTS). Traditional real-time RT-PCR and HTS with Ion Torrent PGM detected the presence of dengue virus serotype 2 (DENV-2). A clinical DENV-2 isolate GZ05/2014 was obtained by culturing the patient serum in mosquito C6/36 cells. The complete genome of GZ05/2014 was determined and deposited in GenBank under the access number KP012546. Phylogenetic analysis based on the complete envelope gene showed that the newly DENV-2 isolate belonged to Cosmopolitan genotype and clustered closely with other Guangdong strains isolated in the past decade. No amino acid mutations that are obviously known to increase virulence or replication were identified throughout the genome of GZ05/2014. The high homology of Guangdong DENV-2 strains indicated the possibility of establishment of local DENV-2 circulation in Guangdong, China. These results help clarify the origin of this epidemic and predict the future status of dengue in China.

Spatial and temporal patterns of dengue in Guangdong province of China.

PubMed

Wang, Chenggang; Yang, Weizhong; Fan, Jingchun; Wang, Furong; Jiang, Baofa; Liu, Qiyong

2015-03-01

The aim of the study was to describe the spatial and temporal patterns of dengue in Guangdong for 1978 to 2010. Time series analysis was performed using data on annual dengue incidence in Guangdong province for 1978-2010. Annual average dengue incidences for each city were mapped for 4 periods by using the geographical information system (GIS). Hot spot analysis was used to identify spatial patterns of dengue cases for 2005-2010 by using the CrimeStat III software. The incidence of dengue in Guangdong province had fallen steadily from 1978 to 2010. The time series was a random sequence without regularity and with no fixed cycle. The geographic range of dengue fever had expanded from 1978 to 2010. Cases were mostly concentrated in Zhanjiang and the developed regions of Pearl River Delta and Shantou. © 2013 APJPH.

The revised WHO dengue case classification: does the system need to be modified?

PubMed

Hadinegoro, Sri Rezeki S

2012-05-01

There has been considerable debate regarding the value of both the 1997 and 2009 World Health Organization (WHO) dengue case classification criteria for its diagnosis and management. Differentiation between classic dengue fever (DF) and dengue haemorrhagic fever (DHF) or severe dengue is a key aspect of dengue case classification. The geographic expansion of dengue and its increased incidence in older age groups have contributed to the limited applicability of the 1997 case definitions. Clinical experience of dengue suggests that the illness presents as a spectrum of disease instead of distinct phases. However, despite the rigid grouping of dengue into DF, DHF and dengue shock syndrome (DSS), overlap between the different manifestations has often been observed, which has affected clinical management and triage of patients. The findings of the DENCO study evaluating the 1997 case definitions formed the basis of the revised 2009 WHO case definitions, which classified the illness into dengue with and without warning signs and severe dengue. Although the revised scheme is more sensitive to the diagnosis of severe dengue, and beneficial to triage and case management, there remain issues with its applicability. It is considered by many to be too broad, requiring more specific definition of warning signs. Quantitative research into the predictive value of these warning signs on patient outcomes and the cost-effectiveness of the new classification system is required to ascertain whether the new classification system requires further modification, or whether elements of both classification systems can be combined.

Imported dengue from 2013 Angola outbreak: Not just serotype 1 was detected.

PubMed

Abreu, Cândida; Silva-Pinto, André; Lazzara, Daniela; Sobrinho-Simões, Joana; Guimarães, João Tiago; Sarmento, António

2016-06-01

All the reports from Angola's 2013 dengue outbreak revealed serotype 1. However, previously dengue serotypes 1-4 have been reported in Africa and in 2014 serotype 4 was reported in Angola. To report dengue serotypes in patients returning from Angola during 2013 outbreak. Retrospective, cross-sectional study. We serotyped the dengue by an in house Polymerase Chain Reaction technique in randomly selected cases. From the 2013 Angola's dengue outbreak we treated 47 adult patients. None had history of past dengue. A combo kit test for dengue revealed positive NS1 antigen in 39 and IgM antibodies in 8. From 17 randomly patients tested by RNA Real Time-PCR, 11 were positive: 7 for DENV-1, 2 for DENV-2, 1 for DENV-3 (co-infected with DENV-1) and 1 for DENV-4. None had a complicated or fatal evolution. Unlike previous reports the 4 serotypes were detected, and this resulted in a different epidemiological situation, raising the risk of future outbreaks of severe dengue. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of dengue fever risk using geostatistics model in bone regency

NASA Astrophysics Data System (ADS)

Amran, Stang, Mallongi, Anwar

2017-03-01

This research aim is to analysis of dengue fever risk based on Geostatistics model in Bone Regency. Risk levels of dengue fever are denoted by parameter of Binomial distribution. Effect of temperature, rainfalls, elevation, and larvae abundance are investigated through Geostatistics model. Bayesian hierarchical method is used in estimation process. Using dengue fever data in eleven locations this research shows that temperature and rainfall have significant effect of dengue fever risk in Bone regency.

Socio-demographic, ecological factors and dengue infection trends in Australia.

PubMed

Akter, Rokeya; Naish, Suchithra; Hu, Wenbiao; Tong, Shilu

2017-01-01

Dengue has been a major public health concern in Australia. This study has explored the spatio-temporal trends of dengue and potential socio- demographic and ecological determinants in Australia. Data on dengue cases, socio-demographic, climatic and land use types for the period January 1999 to December 2010 were collected from Australian National Notifiable Diseases Surveillance System, Australian Bureau of Statistics, Australian Bureau of Meteorology, and Australian Bureau of Agricultural and Resource Economics and Sciences, respectively. Descriptive and linear regression analyses were performed to observe the spatio-temporal trends of dengue, socio-demographic and ecological factors in Australia. A total of 5,853 dengue cases (both local and overseas acquired) were recorded across Australia between January 1999 and December 2010. Most the cases (53.0%) were reported from Queensland, followed by New South Wales (16.5%). Dengue outbreak was highest (54.2%) during 2008-2010. A highest percentage of overseas arrivals (29.9%), households having rainwater tanks (33.9%), Indigenous population (27.2%), separate houses (26.5%), terrace house types (26.9%) and economically advantage people (42.8%) were also observed during 2008-2010. Regression analyses demonstrate that there was an increasing trend of dengue incidence, potential socio-ecological factors such as overseas arrivals, number of households having rainwater tanks, housing types and land use types (e.g. intensive uses and production from dryland agriculture). Spatial variation of socio-demographic factors was also observed in this study. In near future, significant increase of temperature was also projected across Australia. The projected increased temperature as well as increased socio-ecological trend may pose a future threat to the local transmission of dengue in other parts of Australia if Aedes mosquitoes are being established. Therefore, upgraded mosquito and disease surveillance at different ports should

Optimization and Validation of a Plaque Reduction Neutralization Test for the Detection of Neutralizing Antibodies to Four Serotypes of Dengue Virus Used in Support of Dengue Vaccine Development

PubMed Central

Timiryasova, Tatyana M.; Bonaparte, Matthew I.; Luo, Ping; Zedar, Rebecca; Hu, Branda T.; Hildreth, Stephen W.

2013-01-01

A dengue plaque reduction neutralization test (PRNT) to measure dengue serotype–specific neutralizing antibodies for all four virus serotypes was developed, optimized, and validated in accordance with guidelines for validation of bioanalytical test methods using human serum samples from dengue-infected persons and persons receiving a dengue vaccine candidate. Production and characterization of dengue challenge viruses used in the assay was standardized. Once virus stocks were characterized, the dengue PRNT50 for each of the four serotypes was optimized according to a factorial design of experiments approach for critical test parameters, including days of cell seeding before testing, percentage of overlay carboxymethylcellulose medium, and days of incubation post-infection to generate a robust assay. The PRNT50 was then validated and demonstrated to be suitable to detect and measure dengue serotype-specific neutralizing antibodies in human serum samples with acceptable intra-assay and inter-assay precision, accuracy/dilutability, specificity, and with a lower limit of quantitation of 10. PMID:23458954

Socio-economic, Knowledge Attitude Practices (KAP), household related and demographic based appearance of non-dengue infected individuals in high dengue risk areas of Kandy District, Sri Lanka.

PubMed

Udayanga, Lahiru; Gunathilaka, Nayana; Iqbal, M C M; Pahalagedara, Kusumawathie; Amarasinghe, Upali S; Abeyewickreme, Wimaladharma

2018-02-21

Socio-economic, demographic factors and Knowledge Attitude Practices (KAPs) have been recognized as critical factors that influence the incidence and transmission of dengue epidemics. However, studies that characterize above features of a risk free or low risk population are rare. Therefore, the present study was conducted to characterize the household related, demographic, socio-economic factors and KAPs status of five selected dengue free communities. An analytical cross-sectional survey was conducted on selected demographic, socio-economic, household related and KAPs in five selected dengue free communities living in dengue risk areas within Kandy District, Central Province, Sri Lanka. Household heads of 1000 randomly selected houses were interviewed in this study. Chi-square test for independence, cluster analysis and Principal Coordinates (PCO) analysis were used for data analysis. Knowledge and awareness regarding dengue, (prevention of the vector breeding, bites of mosquitoes, disease symptoms and waste management) and attitudes of the community (towards home gardening, composting, waste management and maintenance of a clean and dengue free environment) are associated with the dengue free status of the study populations. The vector controlling authorities should focus on socio-economic, demographic and KAPs in stimulating the community to cooperate in the integrated vector management strategies to improve vector control and reduce transmission of dengue within Kandy District.