The most serious, life-threatening complication of dengue infection is dengue shock syndrome (DSS), seen primarily in children. Daily platelet counts in children in the early stages of dengue can predict those most at risk for DSS, researchers report in PLOS Neglected Tropical Diseases.
More than a third of the world’s population lives in areas at risk for dengue virus infection, a mosquito-borne illness caused by any of four related viruses. Most of the hundreds of millions of people a year who catch the virus recover after a few days of aching and fever, but in some cases, the disease can cause more severe complications. In children particularly, dengue can progress to dangerous DSS when plasma leaks out of small blood vessels.
In the new work, Phung Khanh Lam, of the Oxford University Clinical Research Unit, Vietnam, and colleagues followed 2,301 children aged 5 through 15 admitted to the Hospital for Tropical Diseases in Ho Chi Minh City for suspected dengue, between 2001 and 2009. Daily blood counts, together with vital signs, symptoms, and physical exam information at presentation, were available for each child, all of whom were enrolled in the first four days of the onset of symptoms. The researchers analyzed which factors were associated with a greater risk of developing DSS.
Among the children in the study, 143 (6 percent) progressed to DSS. Risk factors present at enrolment that boosted a child’s risk of later developing DSS included a history of vomiting, higher temperature, palpable liver, and a lower platelet count. Moreover, daily platelet counts, as well as changes in platelet counts over time, helped discriminate patients who went on to develop DSS. However, the model created based on these results has only moderate predictive value in identifying all patients who go on to get DSS and more research is needed to determine other factors that may be integrated into a more clinically useful prediction model. “Although the study was performed among hospitalized children, the findings may be applicable to the population of children now managed as outpatients during the early phase of their illness in many large cities across southeast Asia,” the researchers say.
PATHOLOGY
“The findings reinforce the view that in the early febrile phase dengue is typically a rather non-specific illness, but also provide strong support for the WHO recommendation to perform daily full blood counts in order to monitor the platelet count closely in these patients.” Powerful dengue neutralizing antibody found A super-potent antibody that requires a minute amount to neutralize the dengue virus has been identified by researchers. The study showed how a newly identified antibody 5J7, is highly effective in killing dengue virus whereby only 10-9 g of antibody is needed to stop the infection of dengue serotype 3 virus. This new finding gives hope for the development of effective dengue treatments.
A new Duke-NUS-led study has identified a super-potent antibody which requires a minute amount to neutralize the dengue virus.
The study, published online on 20 February 2015, in the journal Nature Communications, showed how a newly identified antibody 5J7, is highly effective in killing dengue virus, whereby only 10-9 g of antibody is needed to stop the infection of dengue serotype 3 virus (DENV-3). This new finding gives hope for the development of effective dengue treatments.
Over the last 50 years, the incidence of dengue virus has increased by 30 times worldwide. The virus causes fever, rashes and joint pain and in severe cases, bleeding and shock. It is estimated to be endemic in 100 countries and is a huge burden on healthcare systems. However, till now, there is no licensed dengue vaccine or therapeutic agent due to the presence of four circulating virus serotypes (DENV1-4) complicating their development.
Senior author Associate Professor Shee Mei Lok from Duke-NUS Graduate Medical School Singapore (Duke-NUS) focuses her research on understanding the pathology and structure of the dengue virus to develop effective therapeutics. Her lab has already discovered antibodies that are effective against DENV-1. Her strategy to develop a safe therapeutic is to combine four antibodies that each bind and potently inhibit infection of each of the dengue virus serotypes.
In this recent study, researchers isolated 5J7 from 200 different candidate antibody molecules by studying blood samples from a dengue infected patient.
By examining the virus-antibody complex structure at very high magnification, they showed that each arm of the antibody is surprisingly effective in grabbing three surface proteins on the surface of the virus at the same time. In addition, the sites on the virus where the antibody was bound were critical for the virus to invade cells.
“This kind of binding with the virus has never been observed and it explains why the antibody itself is so highly potent.” said A/Prof Lok, from the Emerging Infectious Diseases Program at Duke-NUS. “The movement of virus surface proteins is highly essential for invading cells -- you can think of antibody 5J7 locking the virus surface proteins, thus strapping the virus.”
While antibody 5J7 has been found to be effective against DENV-3, the remaining two serotypes of dengue virus (DENV-2 and DENV-4) have to be considered. When a patient is infected by one serotype -- this stimulates the production of a variety of antibodies that kills that serotype and that patient will have life-time immunity towards that particular serotype.
However, in this process, the patient will also produce antibodies that will bind the other three if they are infected by them. This may enhance their secondary infection and cause the development of a more severe form of the disease.
“We need to test the efficacy in mouse models first and then move to clinical trials,” said A/Prof Lok about the next step after this promising finding. “We are optimistic that we will make a treatment breakthrough within these few years but antibodies against all the other serotypes have to be identified first.”
- Duke-NUS Graduate Medical School Singapore
(Science Daily)