Dengue Research

There’s been a huge uptick in dengue research since climate change began to double the disease’s range and it started afflicting people in rich countries. Here’s a great database, from Harvard University, that will let you do your own research:

Dengue Occurrence World Wide
Dengue Occurrence World Wide

And here’s a fascinating development in the antigenic properties of the four dengue virus types:

“An international consortium of laboratories worldwide that are studying the differences among dengue viruses has shown that while the long-held view that there are four genetically-distinct types of the virus holds, far more important are the differences in their antigenic properties – the ‘coats’ that the viruses wear that help our immune systems identify them.

Dengue virus infects up to 390 million people each year. Around a quarter of these people will experience fever, headaches and joint pains, but approximately 500,000 people will experience potentially life-threatening complications, including haemorrhage and shock, where dangerously low blood pressure occurs. There are currently no vaccines against infection with dengue virus.

For decades, scientists have thought that there are four genetically-distinct types of the virus, known as serotypes, and that antigenic differences between the types play a key role in the severity of disease, its epidemiology and how the virus evolves – and hence these differences would be important in vaccine design.

When we become infected, our immune system sends out antibodies to try and identify the nature of the infection. If it is a pathogen – a virus or bacteria – that we have previously encountered, the antibodies will recognise the invader by antigens on its surface and set of a cascade of defences to prevent the infection taking hold. However, as pathogens evolve, they can change their antigens and disguise themselves against detection.

One of the unusual aspects of dengue is that in some cases when an individual becomes infected for a second time, rather than being immune to infection, the disease can be much more severe. One hypothesis to explain this is that the antibodies produced in response to infection with one strain of the virus somehow allow viruses of a different strain to enter undetected into cells, implying that antigenic differences between the serotypes are important.

Researchers from the Dengue Antigenic Cartography Consortium, writing in today’s edition of Science, analysed 47 strains of dengue virus with 148 samples taken from both humans and primates to see whether they indeed fit into four distinct types. The researchers found a significant amount of antigenic difference within each dengue serotype – in fact, the amount of difference within each serotype was of a similar order to that between the different types. This implies that an individual infected with one type may not be protected against antigenically different viruses of the same type, and that in some cases the individual may be protected against some antigenically similar strains of a different type.

Leah Katzelnick, a researcher from the Department of Zoology at the University of Cambridge, who began studying dengue after herself contracting the disease, says: “We were surprised at how much variation we saw…” Read more..

And here’s a useful discovery from a team at the University of Texas:

How dengue virus adapts as it travels

GALVESTON, Texas, July 6, 2015 – A researcher from The University of Texas Medical Branch at Galveston is an integral member of a collaborative group that is the first to explain the mechanisms that the Dengue virus has developed to optimize its ability to cause outbreaks as it travels across the globe to new places and revisits old ones. An early online version of this paper detailing the findings has recently been published in Science.

Dengue virus has been spreading throughout warm regions of the world, prompting the virus to adapt to new environments. This diversification in viral strains has resulted in the development of strains that appear associated with greater potential for sparking epidemics. Several dengue outbreaks have occurred when new dengue strains emerged and displaced the native strains that the local population had already developed immunity against. Until now, the mechanisms governing how and why some viral strains are better suited for causing widespread disease has been poorly understood.

The investigators examined the different clades of dengue virus-2 known to be circulating around Puerto Rico in 1994 when a severe epidemic broke out. Investigating the differences between the virus strain that was most commonly seen from 1986 to 1995 and a new, more potent viral strain that was first isolated in 1994 was the key to figuring out why this outbreak occurred.

They identified an interaction between the newcomer virus’s RNA and proteins within the host that allows the virus to bypass the host’s immune response, making it easier for the virus to invade. Based on the findings, the research team devised a model to explain the 1994 dengue outbreak in Puerto Rico.

“This study highlights the critical and oft forgotten role played by non-coding RNAs in the battle between viruses and their human hosts,” said author Mariano Garcia-Blanco, UTMB professor and chair of the department of biochemistry and molecular biology and also professor of emerging infectious diseases at the Duke-NUS Graduate Medical School in Singapore. “It emphasizes the importance of multidisciplinary research: a fabulous marriage of basic RNA biology and clinically informed epidemiology uncovered an unexpected route of virus evolution that explained (and perhaps could predict) epidemic potential.”

Other authors of this paper include Gayathri Manokaran, Esteban Finol, Jayantha Gunaratne, Eugenia Z. Ong, Hwee Cheng Tan, October M. Sessions, Alex M. Ward, Duane J. Gubler and corresponding author Eng Eong Ooi from the Duke-NUS Graduate Medical School; Chunling Wang, and Eva Harris from the University of California, Berkeley and Justin Bahl from the University of Texas School of Public Health, Houston.

This research was supported by the Singapore National Medical Research Council, the Ministry of Health in Singapore, Institute of Molecular and Cell Biology, Agency of Science, Technology and Research in Singapore and the U.S. National Institutes of Health.

Here are some links to dengue research in PLOS1:

Here are more dengue research links from Travel Medicine:

Cited in Scopus: 0
Burke A. Cunha, Sigridh Munoz-Gomez
Travel Medicine and Infectious DiseaseVol. 12Issue 3p293–295
Published online: April 3, 2014
Cited in Scopus: 7
Danilo Tomasello, Patricia Schlagenhauf
Travel Medicine and Infectious DiseaseVol. 11Issue 5p274–284
Published online: August 19, 2013
Cited in Scopus: 1
 Karin Leder, Margot Mutsch, Patricia Schlagenhauf, Christine Luxemburger, Joseph Torresi
Travel Medicine and Infectious DiseaseVol. 11Issue 4p210–213
Published online: July 25, 2013
Cited in Scopus: 0
 Natalie Cleton, Chantal Reusken, Jean-Luc Murk, Menno de Jong, Johan Reimerink, Annemiek van der Eijk, Marion Koopmans
Travel Medicine and Infectious DiseaseVol. 12Issue 2p159–166
Published online: December 2, 2013
Cited in Scopus: 2
 Praveen Nilendra Weeratunga, Manjula Chandragomi Caldera, Inuka Kishara Gooneratne, Ranjanie Gamage, Priyankara Perera
Travel Medicine and Infectious DiseaseVol. 12Issue 2p189–193
Published online: December 12, 2013
Cited in Scopus: 4
 Yasutaka Mizuno, Yasuyuki Kato, Shigeyuki Kano, Tomohiko Takasaki
Travel Medicine and Infectious DiseaseVol. 10Issue 2p86–91
Published online: March 19, 2012
Cited in Scopus: 0
 Aravinthan Varatharaj
Travel Medicine and Infectious DiseaseVol. 12Issue 2p194
Published online: January 31, 2014
Cited in Scopus: 0
 Beuy Joob, Viroj Wiwanitkit
Travel Medicine and Infectious DiseaseVol. 12Issue 2p195
Published online: March 13, 2014
Cited in Scopus: 0
 Viroj Wiwanitkit
Travel Medicine and Infectious DiseaseVol. 11Issue 5p332
Published online: September 10, 2013
Cited in Scopus: 1
 Sadegh Chinikar, Seyed Mojtaba Ghiasi, Nariman Shah-Hosseini, Ehsan Mostafavi, Maryam Moradi, Sahar Khakifirouz, Fereshteh Sadat Rasi Varai, Mahboubeh Rafigh, and others
Travel Medicine and Infectious DiseaseVol. 11Issue 3p166–169
Published online: November 28, 2012
Cited in Scopus: 0
 Marion Delord, Cristina Socolovschi, Philippe Parola
Travel Medicine and Infectious DiseaseVol. 12Issue 5p443–458
Published online: September 14, 2014
Cited in Scopus: 1
 Siu-keung Edmond Ma, Wang Christine Wong, Chi-wah Ryan Leung, Sik-to Thomas Lai, Yee-chi Janice Lo, Kai-hay Howard Wong, Man-chung Chan, Tak-lun Que, and others
Travel Medicine and Infectious DiseaseVol. 9Issue 3p95–105
Published online: June 14, 2010
Cited in Scopus: 1
 Jason M. Blaylock, Ashley Maranich, Kristen Bauer, Nancy Nyakoe, John Waitumbi, Luis J. Martinez, Julia Lynch
Travel Medicine and Infectious DiseaseVol. 9Issue 5p246–248
Published online: July 21, 2011
Cited in Scopus: 11
 David W. Smith, David J. Speers, John S. Mackenzie
Travel Medicine and Infectious DiseaseVol. 9Issue 3p113–125
Published online: June 14, 2010
Cited in Scopus: 2
 Uzma N. Sarwar, Sandra Sitar, Julie E. Ledgerwood
Travel Medicine and Infectious DiseaseVol. 9Issue 3p126–134
Published online: June 28, 2010
Cited in Scopus: 1
 Andreas Neumayr, Christoph Hatz, Johannes Blum
Travel Medicine and Infectious DiseaseVol. 11Issue 6p337–349
Published online: October 31, 2013
Cited in Scopus: 2
 Burke A. Cunha, Arthur Gran, Sigridh Munoz-Gomez
Travel Medicine and Infectious DiseaseVol. 11Issue 1p66–69
Published online: October 22, 2012
Cited in Scopus: 5
 Eleonora Lupi, Christoph Hatz, Patricia Schlagenhauf
Travel Medicine and Infectious DiseaseVol. 11Issue 6p374–411
Published online: November 6, 2013
Cited in Scopus: 2
 Mary Elizabeth Wilson, Lin H. Chen
Travel Medicine and Infectious DiseaseVol. 12Issue 3p205–207
Published online: April 17, 2014
Cited in Scopus: 1
 Kelly Kamimura-Nishimura, Donald Rudikoff, Murli Purswani, Stefan Hagmann
Travel Medicine and Infectious DiseaseVol. 11Issue 6p350–356
Published online: October 28, 2013

India’s Botanical Dengue Drug

India’s botanical Dengue drug is getting world wide attention. At last! India, the home of ayurvedic medicine, has begun work to develop, test and market a botanical drug to treat of dengue, with drug major Sun Pharma announcing its collaborative effort with the International Centre for Genetic Engineering and Biotechnology (ICGEB).
The move follows a March announcement of success in the drug’s initial development stage through a joint project between the ICGEB, the Department of Biotechnology (DBT).

Dengue Mosquito: Aedes Aegypti
Dengue Mosquito: Aedes Aegypti

Sun Pharma will fund entire development programme of Cissampelos pariera (Cipa), the botanical drug to treat all strains of dengue. While the pharma giant will pay royalty following commercialisation of the drug, the ICGEB will provide the technical know-how and pre-clinical expertise.
“Using the knowledge of traditional Indian medicine, we explored the indigenous herbal bio-resource to identify plants with pan-DENV inhibitory activity and identified CIPA as a safe, affordable and effective solution,” said Dr Dinakar M Salunke, director, ICGEB, New Delhi.
Given the densely-populated cities and the high prevalence of the mosquito that spreads dengue — aedes aegypti — India is home to close to 50% of the global population estimated to be at risk of dengue. Severe dengue, which can potentially kill, correlates with very high-virus load, reduction in platelet counts and haemorrhage.
The new drug is expected to reduce high-virus load and make the disease milder, leading to fewer hospitalisations. The collaboration aims to explore how the extract prepared from Cipa Linn can inhibit the replication of virus in living cells against dengue infection.
The terms of this agreement permits Sun Pharma’s access to all the intellectual properties of this drug cross 17 countries.
“In tropical countries like India, where dengue outbreaks are significantly intense, a drug for dengue is an unmet public health need. Our partnership with ICGEB aims to develop Cipa as a safe, effective & affordable botanical drug for treatment of dengue,” said Kirti Ganorkar, senior V-P, business development and portfolio management, Sun Pharma, the world’s fifth largest generic pharmaceutical company.
The ICGEB will establish assay systems for development of Cipa for treatment of dengue infection for a pre-defined period of time. The ICGEB will work exclusively with Sun Pharma for the development of this drug, and clinical treatment strategies based on botanical and phyto-pharmaceuticals. Sun Pharma will pay royalties on sales post commercialisation. Other financial details of this agreement are confidential.
Dengue is estimated to costs India over $1.1 billion (about Rs 7,260 crore) annually, with the cost of medical care being nearly $550 million and the indirect cost, in terms of lost wages, being another $550 million. Read more..