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ANOTHER BIG ALARM WITH EBOLA, DENGUE BECOMES INCREASINGLY SERIOUS

News for WSJ DENGUE FEVER

Wall Street Journal
Dengue Fever Researchers in Military Weigh Infecting Volunteers
Wall Street Journal - 23 hours ago

Dengue Fever Outbreaks Strike Asia
Wall Street Journal - 5 hours ago

Dengue Fever Epidemic Neglected Amid Ebola Scare

Dengue Fever Researchers in Military Weigh Infecting Volunteers
http://online.wsj.com/articles/dengue-fever-researchers-in-military-weigh-infecting-volunteers-1415908102
Disease’s Spread Hastens Push to Develop Vaccine, but Concerns Arise

The Aedes aegypti, above, and Aedes albopictusis mosquitoes transmit the viruses that cause dengue fever, according to the Centers for Disease Control and Prevention. ASSOCIATED PRESS
By SHIRLEY S. WANG
Nov. 13, 2014 2:48 p.m. ET

Scientists at Walter Reed Army Institute of Research are considering resurrecting a research program that would infect healthy people with dengue fever, the potentially deadly mosquito-borne disease that has no specific drug treatment.
The tests raise ethical issues, but advocates say they are offset by the need to halt the dramatic growth in the disease. As many as 50 million people a year are infected with dengue, a 30-fold increase in the last 50 years. The disease causes 22,000 deaths each year, mainly among children, the World Health Organization says.
“Here you’re way out on the end of the risk-benefit spectrum,” said Arthur Caplan, director of the division of medical ethics at New York University’s Langone Medical Center. “It’s ethical to do it, but you have to go in with your eyes wide, wide open.”
The purpose of such a study, known as the “human infection” or “human challenge” model, is to see which viral strains cause mild dengue illness in people. The strains that make people sick are used to test potential vaccines and drugs, possibly leading to prevention and treatment of the disease.
The human-infection model is commonly used by researchers and drug and vaccine makers to study other diseases, like malaria, flu and infectious diarrhea. But the stakes are higher with dengue because there is no antiviral medication available to treat it.
Vaccine trials, by contrast, are set up to test whether the vaccine works and is safe, not to purposely sicken participants, say experts. For instance, those in a newly launched clinical trial to test an Ebola vaccine in Switzerland, which has spurred global interest, are being injected with only a portion of the virus that comes from an animal, which shouldn’t cause the person to get the disease.

With proper medical care, which consists of pain relievers and fluids, the mortality rate for dengue is much less than 1%. But with poor treatment, death can result in about 20% of cases, according to Stephen J. Thomas, deputy commander for operations at Walter Reed Army Institute of Research.
Research groups around the world have reported infecting small numbers of patients with dengue virus since early in the 20th century—about 670 volunteers in total—with no deaths. The U.S. military has long studied diseases like dengue because of the risk they pose to soldiers.
About 15 years ago, Walter Reed researchers conducted two human dengue challenge trials on 15 military and civilian volunteers with oversight from the U.S. Food and Drug Administration. Some of those challenge viruses validated in the trials were later used in dengue vaccine trials. The virus was isolated from patients who had been sickened in the field, then grown in a lab—this weakens the virus—then purified, formulated and injected into the arms of healthy volunteers, according to Arthur Lyons, an infectious-disease physician who led dengue and other infectious-disease research at the Maryland-based Walter Reed Army Institute of Research for decades.
After those trials were conducted, the program was shelved because it looked like a vaccine would soon be developed. Instead, that vaccine candidate stalled, leaving researchers “back where we were,” said Dr. Thomas.
Over the last 2½ years, the Army has “reinvigorated” its dengue human challenge program to prepare for testing in volunteers again, according to Dr. Thomas, one of the heads of the research.
Dr. Thomas said he would like to start testing volunteers in the first half of 2015, but several hurdles remain, including approval by the FDA and various ethics committees. Participants must demonstrate that they understand the risks of the research before they can participate. They will be carefully screened about their health and willingness to comply with strict monitoring standards, including possibly being in a hospital ward for days. During the challenge, they will be closely cared for, say researchers.
“It’s got to be moral and legal and ethical,” Dr. Thomas said in an interview. “If it’s not, we don’t do it.”
Finding volunteers for past dengue studies hasn’t been difficult, say researchers who conducted the studies. The volunteers are paid, with ethics committees carefully weighing what would be reasonable and what would be considered coercive. Dr. Caplan, the ethicist, said that generally an amount that would lead participants to dismiss the risks is too much. Volunteers also must fully understand the risks. The study may also face increased suspicion by the public because the military is conducting it, said the researchers. Compensation is likely to be in the thousands of dollars but must be approved by an ethics committee, according to Dr. Thomas.
Dengue has spread from nine countries before 1970 to more than 100 currently, according to WHO. Major outbreaks this year have occurred in Guangdong Province in southern China, with more than 41,000 confirmed cases, and the Taiwanese city of Kaohsiung, with over 8,000 cases so far, the worst in several decades.
Dengue vaccine development is difficult for a number of reasons, and progress has been slow. For one thing, there are four known strains of dengue that sicken humans, but effective combination vaccines are difficult to make. Animals don’t react to dengue the same way as humans, so human vaccine trials are critically important in the development of dengue vaccines in particular.
Drug makers continue to try to develop a vaccine for dengue. Sanofi SA published results last week from its late-stage trial of a vaccine showing efficacy of about 60%. The rate is considered modest, according to Dr. Thomas, who wasn’t involved in the vaccine’s development but wrote an editorial to accompany the study in the New England Journal of Medicine. This was conducted on 20,869 children in five Latin American countries where dengue is common.
Conducting clinical trials on people who get infected naturally with dengue can cost hundreds of millions of dollars and are difficult to do. It is hard to find participants for such trials because the typical outbreak is over before approvals are granted, according to Cameron Simmons, a professor of infectious disease at the University of Melbourne who spent more than a decade studying dengue in Vietnam.
Using humans to test a vaccine in a carefully controlled laboratory setting allows scientists to understand whether it will be effective and can help companies decide whether to pursue development of an experimental candidate or not. Human challenge trials may have just tens of patients rather than thousands in the field, said Dr. Simmons.
In the previous dengue experiments, no one had a serious case of the disease, but several participants suffered a variety of dengue symptoms, including high fever, pounding headaches and muscle and joint pain, according to Dr. Lyons, who led one of those trials.
“I would not wish that on my worst enemy,” said Dr. Lyons, who had dengue fever as a child while living in the Philippines.
Write to Shirley S. Wang at [e-mail]

Dengue Fever Outbreaks Strike Asia
http://online.wsj.com/articles/dengue-fever-parts-of-asia-battling-record-outbreaks-of-potentially-deadly-disease-1415972903?tesla=y&mg=reno64-wsj
Southern China, Japan, Taiwan Battle Potentially Deadly Disease

Workers spray insecticide at Yoyogi Park in Tokyo as Japan and other countries in Asia deal with record outbreaks of the mosquito-borne illness known as dengue fever. AGENCE FRANCE-PRESSE/GETTY IMAGES
By SHIRLEY S. WANG
Nov. 14, 2014 8:48 a.m. ET

Though much of the world is focused on the Ebola virus, pockets of Asia are struggling with record outbreaks of a mosquito-borne infectious disease called dengue fever, which has no specific drug treatment.
Guangdong Province in southern China is facing its largest outbreak of the virus in more than 20 years. There have been more than 44,000 confirmed cases in Guangdong, with more than 15,500 people hospitalized and six deaths as of Nov. 12, according to the Provincial Health and Family Planning Commission.
On Nov. 3, the U.S. Centers for Disease Control and Prevention warned travelers to the region about the outbreak, advising them to prevent mosquito bites.
The Taiwanese city of Kaohsiung, with more than 9,000 cases, is battling its largest-ever outbreak of laboratory-confirmed infections. In Hong Kong on Nov. 7, officials confirmed a third case of locally acquired dengue, after last month discovering its first in four years. Earlier this fall, Japan faced its first outbreak in 70 years.
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In Kaohsiung, “the number will exceed 10,000 in the near future,” said Min-Nan Hung, a medical officer at Taiwan’s Centers for Disease Control, in an interview. “Fortunately, the turning point was noticed just a few days ago and the incidence of dengue cases seemed decreasing.”
Officials in Hong Kong expressed concern about finding multiple locally acquired cases of dengue. Though a fair number of its residents contract dengue fever each year, nearly all are infected while traveling abroad. As of Nov. 13, 102 cases of dengue had been confirmed in the city this year, 99 of which originated elsewhere, officials said Friday.
“The Centre for Health Protection is very concerned about the recent occurrence of two local confirmed cases of dengue fever,” said Wing-man Ko, Secretary for Food and Health, at a briefing earlier this month. “Even a single local case of dengue fever is enough to prove that certain populations of mosquitoes are carrying the virus of dengue fever, therefore we have to continue our effort in mosquito control.”
While the virus can’t be spread directly from person to person, a mosquito that has bitten an infected human can transmit the disease to others.
Within a few days of the first locally acquired case of dengue in Hong Kong, which is known for its meticulous public-health and mosquito-control practices, officials had questioned about 300 people in the vicinity of the place where the patient was believed to have contracted the illness and other sites he had frequented, and held two meetings to educate the public about the virus.
Dengue fever cases world-wide have climbed dramatically since the 1960s, with some 50 million people infected annually. Some 500,000 are estimated to contract more-severe dengue that requires hospitalization, leading to about 22,000 deaths each year, according to the World Health Organization.
The virus is regularly found in several countries across southeast Asia, including Thailand, Vietnam, Indonesia and the Philippines, but less commonly strikes more-affluent countries that employ tight mosquito-control strategies. When it does, however, more people tend to fall ill because they don’t have the immunity that many in endemic countries have built up.
“There’s a very good chance if dengue-infected mosquitoes feed on anyone in Japan or South China, that person will get infected,” said Cameron Simmons, a professor of infectious disease at the University of Melbourne who studies dengue.
The economic and public-health impact of dengue in Southeast Asia is substantial, with one analysis published last year in PLOS Neglected Tropical Diseases suggesting its disease burden outstrips that of hepatitis B, upper respiratory infections and ear infection in the region.
Predicting which areas will experience dengue outbreaks and why those hot spots crop up is difficult. One factor is weather, which has been warmer and rainier than normal, creating better breeding grounds for mosquitoes. Experts in Taiwan and mainland China say climate conditions have contributed to the current outbreaks in those areas.
Mosquitoes also tend to hatch after a shorter period and live longer in urban areas compared with those in rural areas, which may exacerbate the problem in cities, according to recent research by Xiao-Guang Chen, head of the department of pathogen biology at Southern Medical University in Guangzhou, China. The work was published Thursday in PLOS Neglected Tropical Diseases.
There are four known types of the dengue virus, and the strains responsible for illness wax and wane cyclically. In regions where dengue is common, one or two strains tend to dominate for three to four years at a time, according to Dr. Simmons. People in the region appear to acquire immunity for those strains and the number of cases will dip for a few years before another strain takes over and infections flare up again.
Taiwan, for instance, experiences an outbreak every four years or so, according to the Taiwan CDC’s Dr. Hung. However, this year’s outbreak is much larger than predicted, he said. In 2010, there were just 1,000 cases on the island, Dr. Hung said.
Treatment for dengue includes rest and fluids and the use of pain relievers with acetaminophen, according to the U.S. CDC.
Write to Shirley S. Wang at [e-mail]

Dengue Fever Epidemic Neglected Amid Ebola Scare
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Jessica Berman
November 13, 2014 7:10 PM
As the Ebola epidemic rages on in western Africa, there’s concern that another disease - which sickens and kills more people globally - is largely being ignored. Dengue fever, which is transmitted by mosquitoes, continues to spread in countries, including India and Malaysia, where nearly half of the world’s population resides. But a long-sought vaccine offering some protection against dengue may soon become available.
Dengue fever causes debilitating flu-like symptoms, rashes, headaches and severe muscle and joint pains. For that reason, the infection is sometimes called “breakbone disease.” Like Ebola, dengue is considered a hemorrhagic disease, resulting in death in the worst cases.
Scott Halstead is senior scientific advisor to the Dengue Vaccine Initiative, an international consortium of scientists and lay people dedicated to the development of a vaccine.
Unlike Ebola, which - in the current epidemic - has so far infected more than 14,000 people in West Africa, Halstead says the scope of dengue is enormous, with up to 100 million infections every year, mostly across Asia.
“I think people in the dengue field feel, 'Golly, ooh, we’re going to be pushed into the shadows.' But because hundreds of thousands, maybe millions, of people require clinical care, it’s a problem. It’s in your face but it’s all over the place," said Halstead.
There are four dengue viruses, all spread by mosquitoes. Surviving infection by one strain provides lifelong immunity against that type but does not protect the person from future infection by the other strains.
Two years ago, a candidate vaccine developed by the French pharmaceutical company Sanofi Pasteur was tested in a group of 4,000 Thai schoolchildren and did not perform as well as hoped. Only 30 percent of the children were protected against infection. The researchers' goal was a vaccine that was 70 percent effective against all types of the dengue virus.
Now, in advanced clinical trials conducted in five Latin American countries involving almost 21,000 healthy children, the company is reporting promising results with the same vaccine.
In an article published early this month in the New England Journal of Medicine, Sanofi reports the vaccine offered 60 to 80 percent protection, resulting in fewer hospitalizations. The children were followed for two years to see if they came down with the disease.
Halstead says the drug seems to work best in those who have already been infected with one of the dengue viruses.
“So this seems to be what this efficacy is largely due to, which is boosting the immunity of people who are already partially immune," he said.
Halstead says the vaccine failed in Thailand because most of the treated kids who became infected were stricken with dengue type 2, the strain of the virus that’s proven to be the most difficult of the four to prevent.
With future clinical trials planned, Sanofi researchers hope to learn more about how the vaccine protects against dengue fever, with an eye toward improving its effectiveness.