The Birth of Ebola

May 1, 2015

By Medical Discovery News

Colorized micrograph of Ebola by Dr. F.A. Murphy

For most Americans, the Ebola scare seems to have come and gone, but that doesn’t mean the outbreak is over in Africa or that we’ve seen the last of the virus, especially considering its history. Scientists believed that Ebola is relatively new as far as viruses go – only 10,000 years old. However, ancient animal bones show that Ebola appeared between 16 and 23 million years ago, perhaps even earlier.

The Ebola virus was discovered in 1976 during two outbreaks in what was then called Northern Zaire (now the Democratic Republic of the Congo) and Southern Sudan. The outbreaks were actually caused by two different strains of the Ebola virus named Zaire and Sudan, with 90 and 50 percent mortality rates respectively. Since then, three other strains have been identified: Tai Forest, Bundibugyo, and Reston, which is the only one that doesn’t affect people. Overall, there have been 27 outbreaks, but the current outbreak that started in March 2014 is by far the worst, infecting almost 25,000 people and killing over 10,000, thereby making it the world’s first Ebola epidemic.

Ebola is a member of the filovirus family, which also includes the Marburg virus discovered in 1967. Filoviruses are zoonotic, meaning they replicate in other animals, their natural reservoirs, before transmitting to humans. The Ebola virus’s natural reservoir is African fruit bats, so it can transfer to humans who come into contact with an infected bat or another species that has been infected, such as chimpanzees, antelope, and porcupine. Then the virus can spread from person to person.

New research into the origins of filoviruses shows that they have evolutionary ties that go back millions of years. Scientists tracked the viruses’ origins by looking for pieces of their genetic information in fossilized animal bones. While using the bones to study the genomes of ancient voles and hamsters, they found the same pieces of the viruses’ genetic material in the same locations in both rodent species. This suggests that the viruses have existed at least as long as the two species have.

Given the billions of bases each animal has in its genome, it is highly unlikely that these fragments of viral genetic information would have been inserted in exactly the same locations during different infections. Scientists therefore concluded that the virus had infected a common ancestor of these two rodents sometime before the Miocene Epoch, 5-23 million years ago, around the time the great apes arose. Furthermore, the viral genetic elements more closely resemble Ebola than Marburg, meaning the two viruses had already diverged from each other. Sometime before then, the two viruses shared a common ancestor that has not yet been identified.

This means that these viruses have been coevolving with mammals for millions and millions of years, much longer than previously believed. An understanding of the origins and evolution of filoviruses could help us better prevent outbreaks of them and hopefully even create a vaccine that would be effective against all of them.

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The Berlin Patient

Feb. 27, 2015

By Medical Discovery News

Millions of people around the world are infected with HIV, the virus that causes AIDS, but only one has ever been cured. Known as the “Berlin Patient,” Timothy Ray Brown is a 48-year-old American living in Germany. Scientists and physicians have wondered how he was cured, and some recently published studies in monkeys have provided one clue.

Brown had been HIV positive since 1995. When HIV infects the body’s cells, it integrates its genetic information into cells, making the virus a permanent part of the host’s genetic information. Brown’s HIV was held at bay by antiretroviral drugs that have made this infection survivable.  However, in 2006 he was diagnosed with acute myeloid leukemia (AML), a cancer unrelated to HIV. AML affects a group of blood cells in bone marrow called the myeloid cells. Brown underwent grueling chemotherapy that failed. In the hope of saving his life, he received two bone marrow transplants. The year of his first transplant, he stopped taking the antiretrovirals, which would normally cause a patient’s HIV levels to skyrocket.

Yet, years later, there is no sign of the virus returning. Only traces of HIV’s genetic material have been found in his blood, and those pieces are unable to replicate. The big question now is: how was this accomplished?

His treatment for AML included three different factors that could have individually or collaboratively resulted in curing his HIV infection. First, in preparation for a bone marrow transplant, a patient is treated with a combination of chemotherapy and whole body radiation to eliminate the entire immune system in preparation for receiving a new one. Second, Brown received blood stem cell transplants from a person with a defective cell surface protein, CCR5, which is what HIV uses to enter cells. People with a CCR5 mutation are resistant to HIV infection. Third, his new immune system may have eliminated the virus and remnants of his old immune system that harbored it in something called a graft versus host reaction.

In an experiment to determine how Brown was cured of HIV, scientists isolated blood stem cells from three Rhesus Macaque monkeys and put them into cold storage. They then infected those monkeys as well as three control monkeys with an engineered version of HIV. Soon after infection, all six monkeys were treated with a cocktail of drugs, and just like in humans, the levels of the virus soon declined. A few months later, the first three monkeys underwent radiation treatments to eliminate their immune systems, and then their immune systems were restored using their own stem cells from storage. Months later, the antiretroviral drugs were withheld from all six monkeys, and the virus came roaring back in five of them. One of the monkeys who underwent the stem cell transplant did not have the virus return in its blood, but it was detected in some tissues.

This experiment established that the destruction of immune system prior to bone marrow transplant was not sufficient to eliminate the virus, so the selection of bone marrow cells resistant to HIV infection and/or the graft versus host reaction may be the reason Brown was cured of HIV. Further studies are needed before we will know exactly how HIV can be cured.

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Quick Diagnosis for Early Treatment

Dec. 12, 2014

By Medical Discovery News

Quick Diagnosis for Early Treatment

The time it takes to test for the cause of an infection ranges from minutes to weeks. A new generation of biosensors may change that, as they are being developed to identify the viral, bacterial, or fungal origin of an illness within a few hours, allowing physicians to begin the correct treatment sooner.

Many infections have symptoms that resemble the flu, such as HIV, the fungal infection coccidioidomycosis, Ebola, and even anthrax. This makes it very difficult to make a diagnosis. The emergence of new microbial pathogens such as SARS and MERS and bacterial resistance to antibiotics only adds to the fight against infectious agents. Scientists like Louis Pasteur and Robert Koch developed the traditional method for diagnosing infectious disease about 150 years ago, and modern methods have improved their discoveries.

Viruses, bacteria, and fungi have genetic information contained in DNA, RNA, or both. Each strand of DNA or RNA is made of four kinds of building blocks called nucleotides: adenine (A), cytosine (C), guanine (G), and thymine (T) in DNA or uracil (U) in RNA. Every species has a unique genetic code as seen in its arrangement of nucleotides, and by unlocking that code scientists can determine their identity. Each of the nucleotides has a different molecular weight, so the number of each nucleotide in a strand of DNA or RNA can be determined by measuring it on a device called a mass spectrometer. This can identify a microbial pathogen faster than the traditional culturing method, and can also identify those that can’t be grown in a lab.

However, the massive amount of DNA and RNA in a patient’s own cells complicates things. To tackle this problem, inventors of the new biosensor have coupled a mass spectrometer with polymerase chain reaction (PCR) to amplify any piece of genetic information that matches a known sequence from a pathogen. The sensor can then detect a very broad array of potential pathogens simultaneously.

Scientists have been very careful in selecting the unique genetic regions of various pathogens for this test. Once the PCR is used to amplify pieces of potential pathogens in the sample, the mass spectrometer spits out a series of numbers that can be cross-referenced to a database of over 1,000 pathogens that cause human disease in just a few hours.

For example, two children were hospitalized with flu-like symptoms in Southern California in 2009. They tested positive for the flu virus, but doctors did not know which strain of the flu they had. The new sensor analyzed their samples and revealed that both children were infected with H1N1, otherwise known as swine flu, which was not circulating at that time. H1N1 became a pandemic strain with cases all around the world.

This new technology represents a universal pathogen detector, capable of identifying the organism responsible for a person’s illness in just a few hours. Networking the detectors between hospitals and health departments would quickly identify outbreaks and possibly save lives.

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Can Measles Save Us from Cancer?

Nov. 14, 2014

By Medical Discovery News

Red blood cells

Today, the words measles, mumps, and rubella (MMR) sound foreign to children. But before a vaccine prevented these three viruses, three to four million American children contracted measles, a possibly serious respiratory disease that can lead to pneumonia, and 40 percent of them required hospitalization each year. The vaccine is 95 percent effective, and in 2012 only 55 cases of measles were reported in the U.S., mostly due to traveling abroad.

Now, a study has demonstrated that the measles virus might actually be a useful treatment, for cancer. It sounds strange – using one serious disease to fight off another – but scientists have found a way to direct the cell-killing powers of viruses to cancer cells. The use of viruses to destroy cancer cells, called oncolytic virotherapy, has been investigated since the 1950s. Other viruses such as herpes and pox have also been used as treatments for other diseases, but the measles virus’s potential to fight cancer is very promising.

The Mayo Clinic in Rochester, Minn., utilized a modified measles virus called MV-NIS. To create this version of the virus, scientists inserted a gene for the protein sodium iodide symporter. This protein helps concentrate iodine in the human thyroid. Therefore, when this genetically engineered measles virus infects tumor cells and replicates, it produces this protein that binds to and concentrates iodine.

This is important because researchers can then inject a patient with radioactive iodine, which shows up on a 3-D imaging technique called SPECT-CT. Using the images, they can observe where cancer cells are at any site in the body. The engineered virus attacks and kills tumor cells but leaves normal cells alone. This works because the virus detects a protein called CD46 on the surface of a cancer cell, then enters the cell and replicates itself, killing the cancer cell.

The first clinical trial consisted of only two myeloma patients who had exhausted all other treatment options. Each patient was injected with one ultra-high dose (the equivalent of 100 million doses of the vaccine) of MV-NIS intravenously.

The results were astounding. The number of myeloma cells in both patients dramatically declined. One patient became cancer free and has remained so, while the other patient’s life was prolonged during this late-stage cancer. Advanced myeloma affects plasma cells, a type of white blood cell that produces antibodies, and is difficult to treat so this result is unprecedented.

MV-NIS is not yet ready for widespread use, but scientists will continue to build off this newfound virotherapy. Already, they plan to experiment with using another radioactive iodine molecules to additionally attack the tumor cells, uniting virotherapy with localized radiation treatment for myeloma. Stay tuned for updates on this promising discovery.

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A Real Ice Monster

July 4, 2014

By Medical Discovery News

From the ice, scientists hauled a monster of unimaginable size. It was larger than any of its kind, and it was alive. Luckily, it wasn’t the Yeti, but Pithovirus sibericum, an abominable snow virus of sorts.

P. sibericum is the largest virus ever discovered. It’s about 1.5 micrometers, larger than some bacterium (a single-celled organism). All things considered though, it’s still microscopic – 1,333 copies of P. sibericum would fit on top of a pin. Luckily, this gigantic virus only infects amoebas, single-celled protozoans that live in bodies of water including lakes, ponds, streams, rivers, and even puddles. Some amoebas are associated with diseases such as dysentery.

This newly discovered virus was named P. sibericumbecause it was found in a sample of permafrost from Siberia, hence the word sibericum. The scientists who discovered it were French, and they were inspired by its shape to call it a Pithovirus from the ancient Greek word pithos, which were large containers used to store wine. They estimate the virus had been in the deep freeze for at least 30,000 years before they resurrected it this year. In 2012, the French scientists also resurrected an ancient plant from fruits buried in the same Siberian permafrost, which led them to search for the virus.

P. sibericum is unique in many ways beyond its record-breaking size. It is oval-shaped with a thick wall and a hole in one end. It has a distinctive honeycomb structure that caps the opening. Most viruses tightly pack their genetic information inside, but P. sibericum has a surprisingly small genome for a virus that big. Viruses one-third its size store two to three times more gene bases. Only about one-third of its proteins have any similarity to those of other viruses.

It is not, however, the first giant virus. Mimivirus was the first large virus ever found, reported in 2003. Previously, the record for largest virus went to Megavirus chilensis, which was found in water samples from Chile.

Just like Mimiviruses and Megaviruses, Pithoviruses are taken up by their amoebic hosts and once inside, they release their proteins and their genetic information. They then commandeer the host cell to produce hundreds of new viral particles, which are released when the host cell ruptures.

Interestingly, another giant virus called Marseillevirus also infects amoebas. Its genome contains a collection of genes found in similar viruses, bacteriophage viruses that infect bacteria, amoebas, and cells from the animal, plant, and fungus kingdoms. This suggests that amoebas may be acting as vessels for mixing genetic information from multiple forms of life. An amoeba could simultaneously be infected with Marseillevirus and bacteria, making it possible to produce complex genomes such as those of the giant viruses.

The resurrection of P. sibericum, a DNA virus long frozen in the now-thawing permafrost, has scientists wondering about undiscovered viruses that might be future threats to human or animal health.

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The Virus in Your Mucus

Dec. 6, 2013

By Medical Discovery News

Though it has a reputation as slimy and gross, mucus is one of the most valuable lines of defense against the bacteria people are exposed to every day of their lives. It exists not only in a person’s nose, but their respiratory, digestive, urogenital, visual, and auditory systems. Now science shows it contains viruses called bacteriophage (phage for short) that attack and kill bacteria.

A virus is a tiny, infectious agent that is made of a protein coating and a core of genetic information. Although viruses can carry genetic information, undergo mutations, and reproduce, they cannot metabolize on their own and thus are not considered alive. Viruses are classified by the type of genetic information they contain and the shape of their protein capsule. There are viruses that infect every living thing on earth. There are even viruses that infect other viruses. Certain viruses that can infect bacteria have been found in mucus.

A healthy adult produces about one to one and one half liters of mucus per day. Mucus consists of water, salts, antibodies, enzymes, and a family of proteins called mucins. Different mucins are responsible for signaling between cells, forming a chemical barrier for protection, and working with the immune system.

Scientists know that wherever bacteria live, there are also phage viruses that infect them. Areas with mucus have 40 phage for every bacterium, while that ratio is only five to one in areas without mucus. To discover what these phage are doing in the mucus, scientists grew two types of lung tissue in the lab: one that produces mucus and one that cannot. When both lung cultures were exposed to the bacteria E. coli, about half the lung cells died. However, when phage that kill the bacteria were added, the lung cells in the presence of mucus survived. This suggests that the combination of phage and mucus can efficiently kill potentially harmful bacteria. 

The researchers also discovered that the outside of phage is studded with antibody-like proteins that attach the phage to the carbohydrates in the mucus. This would help keep the phage where the bacteria are likely to be. The host may use this system to select which phage are localized to the mucus layers and which can be washed away, explaining why beneficial bacteria are not harmed by phage. An important implication of this system is that it controls the microbial populations in the digestive tract, which play a role in obesity, diabetes, and inflammatory bowel disease.

It all started with investigating how phage actually work in the body, and uncovered the revelation that there are in fact beneficial viruses. In the future, this research could be the foundation for designing phage that reside in mucus and combat specific bacteria, or even change the body’s microbiome. 

For a link to this story, click here.

Why Is Polio Still Around?

Dec. 29, 2012

By Medical Discovery News

An Afghan health worker administers the polio vaccine to a child during a vaccination campaign in 2010 in Kabul, Afghanistan

After plaguing humans for thousands of years, polio is on the verge of being wiped out. In 1988, the virus was endemic in 125 countries, but today it exists in only three: Nigeria, Afghanistan, and Pakistan. With scientists so close to eradicating polio, their work exhibits a renewed sense of urgency.

Polio, also called poliomyelitis or infantile paralysis, is caused by a virus that can infect nerves and lead to partial or complete paralysis. Between the 1840s and 1950s, polio epidemics occurred worldwide, paralyzing or killing half a million people each year.

All that changed in the 1950s with the development of polio vaccines. Over twenty years ago, the World Health Assembly resolved to wipe polio from the Earth by 2000. They got pretty close. During that time, healthcare workers immunized over 2 billion children. 

Since humans are the only reservoirs for polio, there’s an opportunity to eliminate the disease yet that hasn’t happened. Why? Inadequate funding is a major barrier. For example, an 18-month action plan devised by the World Health Organization needs $945 million to be fulfilled.

Logistics and politics are even bigger obstacles. Getting the vaccines to children in remote areas is complicated or made impossible by geopolitics, many of which are anti-U.S. or anti-Western. The Taliban has banned vaccinations in northern Pakistan, an area it controls, to protest American drone strikes. In one of the safe havens inside Pakistan, a local community worker helping with the campaign against polio was shot and killed. Just days before, two gunmen shot a Ghanaian doctor working for the WHO and his Pakistani driver, who were also participating in a polio vaccination campaign. 

Some of the violence is driven by a distrust of humanitarian and healthcare workers. A polio vaccine program in Nigeria eight years ago was undermined by rumors that the vaccine was unsafe and part of a nefarious plan to sterilize Muslim children.  

The CIA exacerbated this distrust by using a fake vaccination campaign to locate Osama Bin Laden. It planned to use DNA obtained through administering a Hepatitis B vaccine to identify Bin Ladin’s children and therefore find the terrorist. The ruse enraged locals, along with critics who blame the CIA for damaging the fragile relationship healthcare workers built with local communities in the anti-polio campaign and other vaccine programs. Furthermore, community workers in these areas became even greater targets of terrorist organizations.

Such complications leave polio-free countries at risk for imported cases. Chad, a country bordering Nigeria, has documented a few cases from people crossing the shared border. An outbreak in China in early 2012 that paralyzed 17 children and killed two is believed to have come from Pakistan.

Already this year, over 100 cases of polio have been reported, although they could have been avoided with a 50-cent vaccine. A valiant effort by multiple nonprofit and governmental agencies is now underway to rid the last vestiges of this disease.

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When An Epidemic Becomes a Pandemic

By Medical Discovery News

July 7, 2012

For at least thousands of years, people have suffered flu epidemics and pandemics.  In 412 B.C., Hippocrates described what was likely an influenza epidemic in Ancient Greece. The term influenza comes from 15th century Italy, when people believed stars influenced the illness because it always came in cycles. Soon after, in 1580, the first clear account of a flu pandemic was written. From that point on, records show flu pandemics have been recurring every one to three decades somewhere in the world.

So what is the difference between an epidemic and pandemic? Flu epidemics occur every year because each year the virus comes back just slightly different. In a flu pandemic, a much larger geographic area is affected, sometimes worldwide, when a new strain of the virus infects people for the first time and everyone is susceptible.

The World Health Organization has defined three phases of pandemics. The first, or earliest, is called the Inter-Pandemic period. During this time, no new influenza viruses are detected in humans, but new flu viruses could be circulating in animal populations.

The next level is the Pandemic Alert period. Here, the flu virus is infecting humans but is either incapable or has limited ability for human-to-human transmission. The last is the Pandemic period where there’s widespread and rapid transmission in human populations.

The potential for a flu virus to be capable of causing pandemics lays in its ability to infect many different species including horses, pigs, and birds. As various strains of the flu virus spread from species to species, multiple viruses can infect the same animal, allowing the viruses to exchange genetic information and create a new virus. Once it can infect and efficiently transmit between humans, a pandemic starts.

The annual flu epidemic sickens 20 percent of America’s population and kills 40,000 people, creating a $10 billion loss in productivity and medical costs. Imagine the cost of a pandemic.  The largest recorded was the 1918 Spanish flu pandemic, which killed 675,000 people in America and 20 to 40 million people worldwide.

Today, health officials worry about avian flu (H5N1) and whether, or more likely when, this flu strain will start a new pandemic. The H5N1 virus was first recognized in Hong Kong in 1997.  Since then it has spread extensively throughout Asia and can now be found in the Middle East, Africa, and Europe. The virus is in the Pandemic Alert period with no means yet for extensive human-to-human transmission. As of spring 2012, approximately 600 people have been diagnosed with H5N1 and the mortality rate is an alarming 60 percent.

In order to understand how this virus may attain efficient transmission between people, American and Dutch scientists created a transmissible H5N1 in the lab. The controversial study could help other scientists create a vaccine for when an avian flu pandemic occurs. But others fear this research could provide a “blueprint” for terrorists to create a potential biological weapon.

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