Recent Therapeutic Advancements in Combating Dengue and Glioma

~Written by Kate Lee, MPH (Contact: kate@recombine.com)

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Sanofi-Pasteur's Dengvaxia has been approved for the prevention of the four subtypes of dengue in children over 9 years old and adults under 45 years old. Photo Credit: European Pharmaceutical Review

Infectious and chronic diseases are some of the top priorities in global health. Abundant funding, both from the government and private sector, is poured into therapeutics research to help decrease morbidity and mortality from both types of diseases. For example, recent news has highlighted two promising therapies with the potential to alleviate the global burden of two diseases: dengue fever, an infectious disease, and glioblastoma, a chronic disease.

After 20 years of research, Sanofi, a French pharmaceutical company, developed Dengvaxia, a vaccine to prevent dengue. Mexico is the first country to approve the vaccine for use in children over the age of nine and adults under the age of 45. A clinical trial last year found the vaccine to have an effectiveness of 60.8% against four strains of the virus[1]. Sanofi bypassed European and US regulations and sought regulatory approval for Dengvaxia in dengue-endemic countries. According to their press release, the vaccine, “will be priced at a fair, affordable, equitable, and sustainable price... and may be distributed for free in certain countries”[2].

Dengue is a febrile viral illness that is spread via the bite of an infected mosquito, and is endemic to tropical and sub-tropical climates. According to the World Health Organization (WHO), about 400 million people globally are infected with the dengue virus each year. Prevention has been limited to effective mosquito control and appropriate medical care[3]. These measures are often either ineffectively implemented, or there are limited, or no available medical resources in the community. Dengvaxia has the potential to reduce the burden of dengue, especially in developing countries that are particularly hard-hit with the disease. Future research could be directed towards making the vaccine more effective in children, as severe forms of dengue are the leading cause of illness and death in children in Asian and Latin American countries[3].

As one tropical virus is being prevented, another virus is being used to combat brain cancer. Researchers at Harvard and Yale have teamed up to use vesicular stomatitis virus (VSV) and Lassa virus, to search for and destroy cancer cells in mice[4]. Lassa is a febrile illness, usually transmitted by rodents, and is endemic to tropical and subtropical regions of the world[5]. VSV has been studied for many years and is generally effective in killing cancer cells; it becomes deadly to the patient when it reaches the brain[4,6]. Interestingly, including Lassa virus appears to make VSV safe for cancer therapy in the brain.

Researchers created a Lassa-VSV chimera, an organism that includes the genetic codes of two different organisms, to target glioma, one of the deadliest forms of brain cancer, which accounts for more than 80% of primary malignant brain tumors[7]. Glioblastoma is the most common form of glioma and is associated with poor survival, making this chimeric treatment a potential life saver for many patients. The next step in the treatment development process is primate research to evaluate safety. This is still a long way from the initiation of human trials, and eventual market, but promising nevertheless, for the millions of people globally who are affected by brain cancer.

Dengvaxia and the Lassa-VSV chimera represent recent advancements in therapeutics with potentially significant global impact for brain cancer and dengue respectively - diseases that affect populations in many nations.

References:

1.     Sanofi's Dengvaxia, World's First Dengue Vaccine, Approved For Use In Mexico. International Business Times. http://www.ibtimes.com/sanofis-dengvaxia-worlds-first-dengue-vaccine-approved-use-mexico-2219515. Published December 10, 2015. Accessed December 20, 2015.

2.     World’s First Dengue Vaccine Approved After 20 Years of Research. Bloomberg Business. http://www.bloomberg.com/news/articles/2015-12-09/world-s-first-dengue-vaccine-approved-after-20-years-of-research. Published December 9, 2015. Accessed December 20, 2015.

3.     Dengue and severe dengue. World Health Organization. http://www.who.int/mediacentre/factsheets/fs117/en/. Updated May 2015. Accessed December 20, 2015.

4.     Using a deadly virus to kill cancer: Scientists experiment with new treatment. The Washington Post. https://www.washingtonpost.com/national/health-science/using-a-deadly-virus-to-kill-cancer-scientists-experiment-with-new-treatment/2015/12/07/7d30bc5a-9785-11e5-8917-653b65c809eb_story.html. Published December 7, 2015. Accessed December 20, 2015.

5.     Lassa fever. World Health Organization. http://www.who.int/mediacentre/factsheets/fs179/en/. Updated March 13, 2015. Accessed December 20, 2015.

6.     Viral Therapy in Treating Patient with Liver Cancer. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01628640. Updated July 2015. Accessed December 20, 2015.

7.     Schwartzbaum J A, Fisher J L, Aldape K D, Wrensch M. Epidemiology and molecular pathology of glioma. Nature Clinical Practice Neurology (2006) 2, 494-503. doi:10.1038/ncpneuro0289

Technology is Changing the Way Infectious Diseases are Tracked

~Written by Theresa Majeski (Contact: theresa.majeski@gmail.com; Twitter: @theresamajeski)

Technology is progressively becoming a bigger part of our lives. This holds true in high-income countries and in low- and middle-income countries. By 2012, three quarters of the world’s population had gained access to mobile phones, pushing mobile communications to a new level. Of the over 6 billion mobile subscriptions in use worldwide in 2012, 5 billion of them were in developing countries. The Pew Research Center’s Spring 2014 Global Attitudes survey indicated that 84% of people owned a mobile phone in the 32 emerging and developing nations polled. Internet access is also increasing in low- and middle-income countries. The 2014 Pew Research Center survey indicated that the Internet was at least occasionally used by a median of 44% of people living in the polled countries.

The increase in Internet and mobile phone access has significant implications for how infectious diseases can be better tracked around the world. Although robust and validated traditional methods of data collection rely on established sources like governments, hospitals, environmental, or census data and thus suffer from limitations such as latency, high cost and financial barriers to care. An example of a traditional infectious disease data collection method is the US Centers for Disease Control and Prevention’s (CDC) influenza-like illness (ILI) surveillance system. This system has been the primary method of measuring national influenza activity for decades but suffers from limitations such as differences in laboratory practices, and patient populations seen by different providers, making straightforward comparisons between regions challenging. On an international scale, the WHO receives infectious disease reports from its technical institutions and organizations. However, these data are limited to areas within the WHO’s reach and may not capture outbreaks until they reach a large enough scale.

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Figure 1. CDC Flu View Interactive dashboard: http://gis.cdc.gov/grasp/fluview/fluportaldashboard.html

Compared to traditional global infectious diseases data collection methods, crowdsourcing data allows researchers to gather data in near real-time, as individuals are diagnosed or even before diagnosis in some instances. Furthermore, getting individuals involved in infectious disease reporting helps people become more aware of and involved in their own health. Crowdsourcing infectious disease data provides previously hard to gather information about disease dynamics such as contact patterns and the impact of the social environment. Crowd-sourced data does have some limitations, including data validation and low specificity.

Internet-based applications have resulted in new crowd-sourced infectious disease tracking websites. One example is HealthMap. HealthMap is a freely available website (and mobile app) developed by Boston Children’s Hospital which brings together informal online sources of infectious disease monitoring and surveillance. HealthMap crowd-sources data from libraries, governments, international travelers, online news aggregators, eyewitness reports, expert-curated discussions, and validated official reports to generate a comprehensive worldwide view of global infectious diseases. With HealthMap you can get a worldwide view of what is happening and also sort by twelve disease categories to see what is happening within your local area. 

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Figure 2. HealthMap. http://www.healthmap.org/en/

Another crowd-sourced infectious disease tracking platform was Google’s Flu Trends, and also their Dengue Trends. Google was using search pattern data to estimate incidence of influenza and dengue in various parts of the world. Google’s Flu Trends was designed to be a syndromic influenza surveillance system acting complementary to established methods, such as CDC’s surveillance. Google shut down Flu Trends after 2014 due to various concerns about the validity of the data. As an initial venture into using big data to predict infectious diseases, Flu (and Dengue) Trends have provided information that researchers can use to improve future big data efforts. 

With the increase of mobile phone access around the world, organizations have started using short message service (SMS), also known as text messaging, as a method of infectious disease reporting and surveillance. Text messaging can be used for infectious disease reporting and surveillance in emergency situations where regular communication channels may have been disrupted. After a 2009 earthquake in Sichuan province, China, regular public health communication channels were damaged. The Chinese Center for Disease Control and Prevention distributed solar powered mobile phones to local health-care agencies in affected areas. The phones were pre-loaded with necessary software and one week after delivery, the number of reports being filed returned to pre-earthquake levels. Mobile phone reporting accounted for as much as 52.9% of total cases reported in the affected areas during about a two-month time period after the earthquake. 

Text message infectious disease reporting and surveillance is also useful in non-emergency settings. In many malaria-endemic areas of Africa, health system infrastructure is poor which results in a communication gap between health services managers, health care workers, and patients. With the rapid expansion and affordability of mobile phone services, using text-messaging systems can improve malaria control. Text messages containing surveillance information, supply tracking information and information on patients’ proper use of antimalarial medications can be sent from malaria control managers out in the field to health system managers. Text messaging can also be sent by health workers to patients to remind them of medication adherence and for post-treatment review. Many text message based interventions exist, but there is a current lack of peer-reviewed studies to determine the true efficacy of text message based intervention programs.

Increasing global access to the Internet and mobile phones is changing the way infectious diseases are reported and how surveillance is conducted. Moving towards crowd-sourced infectious disease reporting allows for a wider geographical reach to underserved populations that may encounter outbreaks, which go undetected for a delayed period. While crowdsourcing such data does have limitations, more companies than ever are working on using big data and crowd-sourced data in a reliable way to inform the world about the presence of infectious diseases.

Climate Change and Health, Part 3: Infectious Disease

~Written by Joann Varickanickal (Contact: joann.varickanickal@gmail.com)

This is my final post of a three part series on climate change and health. The first post looked at how climate change will influence the onset and severity of droughts in some areas. The second post examined how some regions are predicted to see an increase in droughts, which would decrease food supply; thus, increasing nutrient deficiencies in those areas. This post will briefly discuss the influence of climate change on waterborne diseases.

Change in climate, including the increases in temperature and changes in rainfall patterns may lead to an increase in waterborne diseases, where insect vectors contaminate the water (Shuman, 2010). Often, higher temperatures are needed for some insects to complete their life cycle. This is the case for mosquitoes, as they live in warm, aquatic habitats (Shuman, 2010). With an increase in temperature and more flooding, there will be an increase in mosquitoes (Shuman, 2010). Thus, there may be an increase in the transfer of dengue and malaria (Ramasamy & Surendran, 2011). These warm, aquatic habitats will also be ideal for snails, which transfer schistomiasis (Ramasamy & Surendran, 2011). Furthermore, with a rise in sea levels, there is likely to be an increase in saline levels (Ramasamy & Surendran, 2011). Certain types of mosquitoes and snails have a high tolerance for salt water and are thus able to breed in water with high salt concentrations (Ramasamy & Surendran, 2011).

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Taken from: Watts N, Adger W N, Agnolucci P, Blackstock J, Byass, P, Cai W, Costello A (2015). Health and climate change: policy responses to protect public health. The Lancet, 6736(15)

The relationship between climate change and health is complex because there are many different contributing factors and there is limited scientific evidence for many regions, several of which are under-resourced (New York Times, 2015). Furthermore, areas of high-resource have not been impacted in the same way, due to advantages as simple as air conditioning (New York Times, 2015). Thus, more scientific evidence is needed, to determine more ways in which climate change could possibly influence the health of a population. More recognition also needs to be given to this issue so that contingency plans can be made for possible outbreaks of diseases that were discussed in this blog post.

References:

Shuman, E. K. (2010). Global Climate Change and Infectious Diseases. The New England Journal of Medicine , 362 (12), 1061-1063.

Ramasamy, R., & Surendran, S. (2011). Possible impact of rising sea levels on vector-borne infectious diseases. BMC Infectious Diseases , 11 (18).

Tavernise, S. (2015, July 13). Unraveling the Relationship Between Climate Change and Health. Retrieved September 10, 2015, from http://www.nytimes.com/2015/07/14/health/unraveling-the-relationship-between-climate-change-and-health.html?_r=0