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In 10 seconds? Dengue is a tropical disease caused by virus, specifically 4 different serotypes, DENV 1-4. The disease is transmitted by a mosquito bite from one person to another. CDC estimates that nearly 40% of world’s populations lives in risk areas being endemic in 100 countries.

What are the symptons? The principal sympton is high fever with a combination of two or more symptons such as severe headache, body pain, low white cells count, mild bleeding and rash. Sometimes, it can develop to dengue hemorrhagic fever (DHF), a dangerous complication that may lead to a persistent high fever, hemorrhagic manifestations and death. In case of suspecting of DHF the person should go to hospital immediately.

What are the current methods to prevent dengue? As the disease is transmitted by mosquitoes, controling vector population has been an important method applied. Mosquito’s eggs need water to hatch, more than that, the eggs can survive months without water and still be viable. In recent years, scientists are trying to control dengue by “creating” genetic modified mosquitoes incapable of transmitting the virus.

A vaccine is a possibility? Since 2016, a live-attenuated tetravalent chimeric yellow fever-dengue vaccine is available. This vaccine is licensed and being tested in several countries but results showed a moderate efficacy (56-61%) among dengue experienced individuals and low efficacy in naiive ones. Right now, several vaccines are in clinical trial and some of them showed promising results. Scientists are confident to have a vaccine in years to come.


Global Epidemiology of Dengue Outbreaks in 1990-2015: A Systematic Review and Meta-Analysis.

Abstract: Dengue is an arthropod-borne infectious disease caused by dengue virus (DENV) infection and transmitted by Aedes mosquitoes. Approximately 50-100 million people are infected with DENV each year, resulting in a high economic burden on both governments and individuals. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, clinical characteristics, and serotype distribution and risk factors for global dengue outbreaks occurring from 1990 to 2015. We searched the PubMed, Embase and Web of Science databases through December 2016 using the term "dengue outbreak." In total, 3,853 studies were identified, of which 243 studies describing 262 dengue outbreaks met our inclusion criteria. The majority of outbreak-associated dengue cases were reported in the Western Pacific Region, particularly after the year 2010; these cases were primarily identified in China, Singapore and Malaysia. The pooled mean age of dengue-infected individuals was 30.1 years; of the included patients, 54.5% were male, 23.2% had DHF, 62.0% had secondary infections, and 1.3% died. The mean age of dengue patients reported after 2010 was older than that of patients reported before 2010 (34.0 vs. 27.2 years); however, the proportions of patients who had DHF, had secondary infections and died significantly decreased after 2010. Fever, malaise, headache, and asthenia were the most frequently reported clinical symptoms and signs among dengue patients. In addition, among the identified clinical symptoms and signs, positive tourniquet test (OR = 4.86), ascites (OR = 13.91) and shock (OR = 308.09) were identified as the best predictors of dengue infection, DHF and mortality, respectively (both P < 0.05). The main risk factors for dengue infection, DHF and mortality were living with uncovered water container (OR = 1.65), suffering from hypotension (OR = 6.18) and suffering from diabetes mellitus (OR = 2.53), respectively (all P < 0.05). The serotype distribution varied with time and across WHO regions. Overall, co-infections were reported in 47.7% of the evaluated outbreaks, and the highest pooled mortality rate (2.0%) was identified in DENV-2 dominated outbreaks. Our study emphasizes the necessity of implementing programs focused on targeted prevention, early identification, and effective treatment.

Pub.: 28 Jul '17, Pinned: 25 Sep '17

Dengue serotype circulation in natural populations of Aedes aegypti.

Abstract: Ae. aegypti is the main vector of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses. The transmission dynamics of these arboviruses, especially the arboviral circulation in the mosquito population during low and high transmission seasons in endemic areas are still poorly understood. We conducted an entomological survey to determine dengue infection rates in Ae. aegypti and Aedes albopictus. These collections were performed in 2012-2013 during a Rio de Janeiro epidemic, just before the introduction and spread of ZIKV and CHIKV in the city. MosquiTrap(©) and BG-Sentinel traps were installed in three fixed and seven itinerant neighborhoods each month over ten months. Mosquitoes were in supernatants pools tested and individually confirmed for DENV infection using RT-PCR. A total of 3,053 Aedes mosquitos were captured and Ae. aegypti was much more frequent (92.9%) than Ae. albopictus (6.8%). Ae. aegypti females accounted for 71.8% of captured mosquitoes by MosquitTrap(©) and were the only species found naturally infected with DENV (infection rate=0.81%). Only one Ae. aegypti male, collected by BG-sentinel, was also tested positive for DENV. The peak of DENV-positive mosquitoes coincided the season of the highest incidence of human cases. The most common serotypes detected in mosquitoes were DENV-3 (24%) and DENV-1 (24%), followed by DENV-4 (20%), DENV-2 (8%) and DENV-1 plus DENV4 (4%), while 95% of laboratory-confirmed human infections in the period were due to DENV-4. These contrasting results suggest silent maintenance of DENV serotypes during the epidemics, reinforcing the importance of entomological and viral surveillance in endemic areas.

Pub.: 27 Jul '17, Pinned: 25 Sep '17

Mosquito control with green nanopesticides: towards the One Health approach? A review of non-target effects.

Abstract: The rapid spread of highly aggressive arboviruses, parasites, and bacteria along with the development of resistance in the pathogens and parasites, as well as in their arthropod vectors, represents a huge challenge in modern parasitology and tropical medicine. Eco-friendly vector control programs are crucial to fight, besides malaria, the spread of dengue, West Nile, chikungunya, and Zika virus, as well as other arboviruses such as St. Louis encephalitis and Japanese encephalitis. However, research efforts on the control of mosquito vectors are experiencing a serious lack of eco-friendly and highly effective pesticides, as well as the limited success of most biocontrol tools currently applied. Most importantly, a cooperative interface between the two disciplines is still lacking. To face this challenge, we have reviewed a wide number of promising results in the field of green-fabricated pesticides tested against mosquito vectors, outlining several examples of synergy with classic biological control tools. The non-target effects of green-fabricated nanopesticides, including acute toxicity, genotoxicity, and impact on behavioral traits of mosquito predators, have been critically discussed. In the final section, we have identified several key challenges at the interface between "green" nanotechnology and classic biological control, which deserve further research attention.

Pub.: 30 Jul '17, Pinned: 25 Sep '17

Progress and Works in Progress: Update on Flavivirus Vaccine Development.

Abstract: Most areas of the globe are endemic for at least one flavivirus, putting billions at risk for infection. This diverse group of viral pathogens causes a range of manifestations in humans from asymptomatic infection to hemorrhagic fever to encephalitis to birth defects and even death. Many flaviviruses are transmitted by mosquitos and have expanded in geographic distribution in recent years, with dengue virus being the most prevalent, infecting approximately 400 million people each year. The explosive emergence of Zika virus in Latin America in 2014 refocused international attention on this medically important group of viruses. Meanwhile, yellow fever has caused major outbreaks in Africa and South America since 2015 despite a reliable vaccine. There is no vaccine for Zika yet, and the only licensed dengue vaccine performs suboptimally in certain contexts. Further lessons are found when considering the experience with Japanese encephalitis virus, West Nile virus, and tickborne encephalitis virus, all of which now have protective vaccination in human or veterinary populations. Thus, vaccination is a mainstay of public health strategy for combating flavivirus infections; however, numerous challenges exist along the path from development to delivery of a tolerable and effective vaccine. Nevertheless, intensification of investment and effort in this area holds great promise for significantly reducing the global burden of disease attributable to flavivirus infection.

Pub.: 30 Jul '17, Pinned: 25 Sep '17

Generation and Characterization of Antinonstructural Protein 1 Monoclonal Antibodies and Development of Diagnostics for Dengue Virus Serotype 2.

Abstract: Dengue virus (DENV) circulates in tropical and subtropical areas around the world, where it causes high morbidity and mortality. There is no effective treatment of infection, with supportive care being the only option. Furthermore, early detection and diagnosis are important to facilitate clinical decisions. In this study, seven monoclonal antibodies (mAbs) recognizing nonstructural protein 1 (NS1) of DENV were generated by hybridoma techniques. These antibodies can be divided into two groups: serotype-specific (DB6-1, DB12-3, and DB38-1) and nonspecific (consisting of antibodies DB16-1, DB20-6, DB29-1, and DB41-2). The B-cell epitopes of DB20-6 and DB29-1 were identified by phage display and site-directed mutagenesis, and its binding motif, WXXWGK, was revealed to correspond to amino acid residues 115-120 of the DENV-2 NS1 protein. A diagnostic platform, consisting of a serotype-specific capture antibody and a complex detection antibody, exhibited a detection limit of about 1 ng/mL, which is sufficient to detect NS1 in clinical serum samples from dengue patients. This diagnostic platform displayed better specificity and sensitivity than two examined commercial NS1 diagnostic platforms. In summary, our results indicate that these newly generated mAbs are suitable for detection of NS1 protein of DENV-2 in clinical samples.

Pub.: 28 Jul '17, Pinned: 25 Sep '17

Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

Abstract: Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance systems accordingly. Targeted studies are needed, especially to better understand the effects of vaccinating seronegative individuals.

Pub.: 13 Sep '17, Pinned: 25 Sep '17