Does studying yellow fever offer Zika clues?

As cases of Zika virus increase there is considerable investigation and research into the virus. One area being looked at for clues is yellow fever virus. A second area involves the use of mouse models.

Zika virus is a member of the Flaviviridae virus family. In one in four people the disease causes a mild illness known as Zika fever, for up to seven days. The symptoms include fever, rashes, joint pain and conjunctivitis. The biggest risks are infected women and babies born with abnormally small heads and brain defects, a condition called microcephaly.

Yellow fever and Zika viruses have a common characteristic in how they can circumvent an insect’s immune response. This is due to the viruses manufacturing proteins that can suppress the immune response in the host. A similar response occurs in people, when we become infected.

For this reason, researchers have been studying mosquitoes and viral infections. This is based on using gene drive, a method targeting specific genes. The idea is to tip the battle at the genetic level in favor of the mosquito. This tranche of research could eventually lead to a human vaccine.

A second wave of research, also from Texas A&M University, College Station, is finding a means to make an infective mosquito undergo altered behavior so that it will not seek out humans to infect.

The research has been published in the journal Proceedings of the National Academy of Sciences. The paper is titled “Yellow fever virus capsid protein is a potent suppressor of RNA silencing that binds double-stranded RNA.”

In a second wave of research, a different group of researchers are seeing whether mice with healthy immune systems could provide new insights into Zika virus pathology and treatment. This is not straightforward due to the changes that animals undergo when they are infected. Mice, however, can, under certain conditions, be used as ideal models for Zika virus research.

The reason for focusing on mice is because studies have indicated that young mice with specific immune system defects are susceptible to Zika infection. By rearing mice (coded C57BL/6) with functioning immune systems that can be successfully infected with Zika, more detailed studies can be made and to provide the basis for testing treatments.

The second research study has been published in the journal PLOS Pathogens. The paper is headed “Zika (PRVABC59) Infection Is Associated with T cell Infiltration and Neurodegeneration in CNS of Immunocompetent Neonatal C57Bl/6 Mice.”

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How Will Genetically Modified Mosquitoes Stop Zika?

Insect repellent, screens on windows, wearing long sleeves -- there is a limit to the precautions that we can take to protect ourselves from viruses that are spread by mosquitoes.

Even by taking all of the above steps, there is no way to have guaranteed protection from mosquito bites.

But, there is one idea that would put an end to all other methods of mosquito repellents.... what if there were no mosquitoes?

That is the idea behind the work of the company Oxitec. They have engineered a mosquito that leads to a decrease in the Aedes aegypti mosquito population. Here is how it works. The company has created a strain of mosquito that is "self limiting" meaning that they have a "death gene" added to their genome that kills their offspring. This strain of mosquitoes is called OX513A, but, they are referred to by the company as 'friendly Aedes.' 

The process starts with the hatching of the OX513A mosquitoes. Then, the males and females are separated from each other. This is easy because males and females are different sizes. Also, the male strain is labeled with a red fluorescent marker, which makes it even easier to tell the difference, in case the size was unclear. After separation, the females are destroyed. Because male mosquitoes do not bite or spread disease, their release will not exacerbate disease spread.  Those same males, upon release, mate with wild females. When the offspring of those matings hatch, they die. 

If enough of these males are released, the total population of mosquitoes will decrease, and eventually become too low to transmit disease. 

Aedes aegypti spread Zika, Dengue fever, yellow fever, and chikungunya virus. One thing that these four infectious diseases have in common is a lack of treatment. If you get them, you wait it out and hope for the best. And, although there is an incredibly effective vaccine for yellow fever, it is widely under produced. So, avoiding mosquito bites is really the only defense against these diseases.   

These mosquitoes have been released in trials in Brazil, Panama (for yellow fever and Dengue) and the Cayman Islands (for Zika.) All of the trials resulted in a 90% reduction of the wild mosquito population. In Brazil, a trial was done in a town of 5,600 people that saw 133 cases of Dengue fever before the trial. After the trial - there was only one case. (1) 

The mosquitoes are expensive and many of them need to be released to see an effect. However, the difference between spending money on the 'friendly Aedes' versus sprays and larvicides is that the mosquitoes actually work.

However, people are cautious to sign up for releasing genetically modified organisms into their community. As more and more people are affected by vector borne illnesses, we will see which is more important - fear of science or infectious disease? 

References: 

1) https://www.technologyreview.com/s/600821/inside-the-mosquito-factory-th...

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Nigeria: Why Zika Virus Spreads in Nigeria - NCDC, Nov 2016

By Nike Adebowale

The Nigerian Centre for Disease Control (NCDC) has said that Zika Virus is spreading in Nigeria as a result of environmental conditions and other related issues.

The centre stated this in a report released to the media on Monday.

"The current epidemiology of Zika in Nigeria has not been well-documented or understood due to paucity of recent data", the report stated.

"The virus shares a similar vector; the Aedes (Steogmyia) mosquitoes, also responsible for other flavivirus infections recorded in Nigeria such as such as yellow fever.

"Consequently, environmental and human behavioural risk factors in areas with reported Zika outbreaks are similar to those found in Nigeria and would thus favour the circulation of Zika.

"Possible cross-reaction with other endemic flaviviruses like yellow fever and dengue; genetic host factors protecting against infection or disease; low vector competence and transmission efficiency; lack of diagnostic testing; and the absence of systematic surveillance are potential limitations to detect on-going transmission of Zika in Nigeria', the report added.

"In the light of above, NCDC plans to initiate surveillance to understand and monitor the epidemiology of Zika virus in Nigeria for the appropriate interventions."

The report also recommended that travellers should be informed of preventive measures before, during and after travelling to areas with Zika transmission.

Intending travellers should also be provided up-to date information of areas with ongoing Zika virus, it concluded.

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Human Trials Begin for Army-Developed Zika Vaccine, Nov 2016

WASHINGTON, Nov. 8, 2016 — A clinical trial began here yesterday at the Walter Reed Army Institute of Research, where 75 participating healthy adults were vaccinated with a Zika virus vaccine that the institute’s scientists developed earlier this year, Walter Reed officials announced today.

Laboratory-confirmed Zika virus disease cases reported to ArboNET by state or territory as of Nov. 2, 2016. ArboNET is a national surveillance system for arthropod-borne virus diseases in the United States, such as those from ticks and mosquitoes. Centers for Disease Control graphic

The Phase 1 trial will test the safety and immunogenicity -- the ability of the vaccine to trigger an immune response in the body -- of the purified, inactivated Zika virus vaccine called ZPIV. The vaccine is being tested at WRAIR’s Clinical Trial Center in Silver Spring, Maryland.

“The Army has moved efficiently from recognizing Zika virus as a threat, producing ZPIV for use in animals and demonstrating its effectiveness in mice and monkeys, producing ZPIV for human testing, and now initiating clinical trials to establish its safety and build the case for subsequent efficacy trials,” Army Col. (Dr.) Nelson Michael, director of WRAIR’s Military HIV Research Program, or MHRP, and Zika program co-lead, said in a statement.

Efficacy refers to the vaccine’s ability to demonstrate a health effect when tested in a clinical trial.

“All of this,” he added, “was done in 10 months.”

Dr. Kayvon Modjarrad, Zika program co-lead and associate director for emerging infectious disease threats at WRAIR’s MHRP, said the Army was able to move so quickly in developing, manufacturing and testing a Zika vaccine “because of its extensive experience with this vaccine platform and longstanding investments in the understanding and mitigation of flaviviruses like yellow fever, dating back to the founding of WRAIR.”

DoD Zika Response

WRAIR officials say this study is part of the Defense Department response to the ongoing Zika outbreak in North and South America and Southeast Asia.

For service members, there are concerns about infection during deployment and travel, but also in the continental United States, where most military installations are concentrated in southern states. There, climate conditions and mosquito populations favor Zika transmission, WRAIR officials say.

Zika virus is transmitted to people primarily through the bite of an infected Aedes species mosquito -- Aedes aegypti, shown here, and Aedes albopictus. The same mosquitoes spread dengue and chikungunya viruses. The mosquitoes typically lay eggs in and near standing water in things like buckets, bowls, animal dishes, flower pots and vases. They prefer to bite people and live indoors and outdoors near people. Mosquitoes that spread chikungunya, dengue, and Zika are aggressive daytime biters, but they can also bite at night. Mosquitoes become infected when they feed on a person already infected with the virus. Infected mosquitoes can then spread the virus to other people through bites. CDC photo by James Gathany

As of Nov. 2, according to the Centers for Disease Control and Prevention, 149 cases of Zika infection were confirmed in the military health system, including four pregnant service members and one pregnant family member.

Zika infection during pregnancy, CDC says, can cause a birth defect of the brain called microcephaly and other severe fetal brain defects.

Other problems have been detected among fetuses and infants infected with Zika virus before birth, such as defects of the eye, hearing deficits and impaired growth. And reports have increased about Guillain-Barré syndrome, an uncommon sickness of the nervous system, in areas affected by Zika, CDC says.

But even Zika infections without symptoms “can lead to severe birth defects and neurological complications,” Zika study principal investigator Army Maj. (Dr.) Leyi Lin said, adding, “A safe and effective Zika vaccine that prevents infection in those at risk is a global public-health priority."

Zika and Other Flaviviruses

Flaviviruses like Zika are found mainly in mosquitoes and ticks and cause widespread morbidity and mortality worldwide. Other mosquito-transmitted viruses that are members of the flavivirus genus include yellow fever, or YF, dengue fever, Japanese encephalitis, or JE, and West Nile viruses, according to the CDC web page.

"We want to assess the safety and immune response of the ZPIV vaccine in JE and yellow fever YF vaccine recipients because these vaccines may alter the response to the ZPIV vaccine,” Lin said.

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VIDEO | 03:04 | Race for the Zika Vaccine: The Army Advantage

“Uniquely,” he added, “illness as a result of natural infection from JE, YF or Zika could be more severe when prior flavivirus infection or vaccination exists. Our study assesses co-vaccination to learn how to reduce risk when protecting against circulating flaviviruses.”

This is important for service members who are vaccinated against other flaviviruses and then stationed in or deployed to areas where Zika is becoming endemic, WRAIR scientists say.

Zika Vaccine Platform

WRAIR’s inactivated flavivirus vaccine platform was the same technology the institute used to create its Japanese encephalitis vaccine, licensed in 2009.

An earlier preclinical study found that rhesus monkeys vaccinated with ZPIV developed a strong immune response and were protected against two strains of Zika virus.

The National Institute of Allergy and Infectious Diseases, or NIAID, part of the National Institutes of Health, helped identify the viral strain used in the ZPIV vaccine, supported the preclinical safety testing and is sponsoring the conduct of this trial.

WRAIR, NIAID and the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority, or BARDA, have established a joint research collaboration agreement to support the vaccine’s development.

The Pilot Bioproduction Facility at WRAIR manufactured the ZPIV vaccine being used in Phase 1 clinical studies, and the Army recently signed a cooperative research and development agreement to transfer the ZPIV technology to Sanofi Pasteur to explore larger-scale manufacturing and advanced development. BARDA recently awarded a six-year contract to Sanofi Pasteur to further develop this vaccine to licensure, according to the WRAIR release.

Transmission electron microscope image of negative-stained, Fortaleza-strain Zika virus, in red, isolated from a microcephaly case in Brazil. National Institutes of Health photo

Other ZPIV Trials

WRAIR’s ZPIV candidate also will soon be part of an NIH trial that began in August. The NIH vaccine contains DNA that instructs volunteers’ cells to make certain Zika proteins that then illicit an immune response. As part of that study, WRAIR’s ZPIV vaccine will be given to volunteers as a booster after they receive the NIH DNA vaccine, WRAIR officials say.

Three more Phase 1 trials using ZPIV are scheduled to begin this year, the WRAIR release noted:

-- St. Louis University researchers, through the NIAID-funded Vaccine and Treatment Evaluation Units network, will examine the optimal dose of the vaccine to be used in larger studies.

-- Beth Israel Deaconess Medical Center and Harvard Medical School researchers will evaluate the safety and immune response from a compressed vaccine schedule.

-- The Ambulatory Center for Medical Research, part of Ponce Health Sciences University in Puerto Rico, will examine the vaccine’s safety and immune response in participants who have already been naturally exposed to Zika or dengue viruses.

The WRAIR trial that began yesterday is sponsored by NIAID and funded by the Army and the Defense Department.

(Follow Cheryl Pellerin on Twitter @PellerinDoDNews)

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Brazil unleashes millions of genetically modified mosquitoes to combat Zika

Mosquitoes are an annoyance to nearly everyone who encounters them, and the little buzzers are responsible for spreading diseases like malaria, yellow fever and, of more recent note, Zika virus. Now scientists in Brazil are fighting back by releasing millions of genetically modified mosquitoes that, ideally, will mate with their wild counterparts and produce offspring with very short lifespans, thus causing disease-carrying family lines to die out within a few generations. Since mosquitoes only live a short time, this could greatly reduce the population of mosquitoes spreading infectious diseases in just a few weeks.

British biotech firm Oxitec is the company leading the charge on the development of genetically modified male mosquitoes belonging to the Aedes aegypti species, which are responsible for the spread of a slew of diseases. The company launched the Friendly Aedes aegypti project in April 2015 in the town of Piracicaba, where some 60,000 people live under daily threat of diseases like dengue fever and Zika virus. Oxitec has been releasing its “self-limiting” mosquitoes across the city, and reporting huge reductions in cases of diseases those mosquitoes spread. After being released into the wild, the male mosquitoes breed with disease-carrying females and produce offspring that die quickly. The company reports that this technique can bring mosquito populations down by 90 percent, according to the results of five field tests conducted between 2011 and 2014.

Despite that good news, there were early concerns that releasing genetically modified mosquitoes may somehow contribute to the spread of viruses like Zika, rather than combat it. Many people blamed Oxitec for the recent Zika epidemic in Brazil, claiming that the aforementioned field tests actually caused the problem. However, experts at the World Health Organization have dismissed that notion in part because the field tests were not conducted in the same region as the Zika hotspot and, while the strategy is controversial, many epidemiologists believe this is the fastest and most effective way to reduce the spread of mosquito-born diseases.

Oxitec is still waiting for approval from the Brazilian government to release their next batch of genetically modified mosquitoes, which would number in the millions. The company contracted with the town of Piracicaba in a $1.1 million deal, and erected what it claims is the “first and biggest factory” for genetically modified mosquitoes there, producing 60 million GM mosquitoes per week. (That’s three times the output of China’s largest mosquito factory, which is working on a similar project.) While Piracicaba is Oxitec’s only customer in Brazil, the company has worked in other parts of the world, doing exactly the same thing in an effort to stamp out mosquito-born diseases that are difficult to treat and, sometimes, deadly. Earlier this year, millions of the company’s little buzzers were released in the Cayman Islands and in Florida as well, two other places where Zika has spread.

Via Gizmodo

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Related: Zika virus found in US mosquitoes for the first time

Do I need a yellow fever injection when I am traveling to Brazil?

Question: I’m going to Brazil. I don’t have a yellow fever jab and according to my research it’s not compulsory.

Should I have one anyway?

A number of nations such as Brazil with a risk of yellow fever transmission will admit the unprotected traveller without formality. Credit: AP

Name withheld

Answer: Yellow fever is a potentially fatal mosquito-borne virus that is prevalent in parts of sub-Saharan Africa and Latin America – including Brazil, apart from the eastern coastal fringe.

Worldwide, yellow fever infects around 200 000 people each year. Most victims start to recover after a few days of flu-like symptoms. But around 15 percent – about 30 000 people a year – die of the disease.

A number of nations such as Brazil with a risk of yellow fever transmission will admit the unprotected traveller without formality; restrictions are much more common when seeking to visit non-yellow fever countries.

The NHS travel medicine site, fitfortravel.nhs.uk, says: “The disease is mainly found in rural areas but outbreaks in urban areas do occur. Vaccination is usually recommended for those who travel into risk areas.”

If you are making a short trip to the popular coastal areas such as Rio and the Bahia region, you could rationally choose not to get a vaccination.

But if you are venturing deeper into Brazil, it is certainly worth getting the jab – which will stand you in good stead for future travel to risk areas.

 On publication of this story, an Independent Traveller reader, back from a recent trip to Brazil, says immigration authorities asked for a yellow fever certificate. Please check with your travel agent or travel clinic when going overseas.

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