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Phages: Bacterial Eaters From Georgia to Fight Antibiotic Resistance

Health + Wellness

By Tim Ruben Weimer

Tanja Diederen lives near Maastricht in the Netherlands. She has been suffering from Hidradenitis suppurativa for 30 years. Its a chronic skin disease in which the hair roots are inflamed under pain — often around the armpits and on the chest.


€3,900 ($4,302) for treatment in Georgia

In August 2019, the now 50-year-old made a radical decision: she discontinued the antibiotics, which were becoming less and less effective. And she traveled to Georgia for two weeks to undergo treatment with bacteriophages (or phages for short).

Such phage therapy is not yet approved in most Western European countries. She paid 3,900 euros out of her own pocket in the hope that the unconventional therapy would help her.

Bacteriophages are viruses that fight against the proliferation of their host bacteria. Therapy with bacteriophages involves the oral administration of a single, isolated type of phage. They attach themselves to their bacterial counterparts in the patient's body in order to survive.

The phages reverse the polarity of the bacterial cell in such a way that it produces further phages, filling up with more and more phages and finally bursts. Then, the released phages attach themselves to other bacteria until all of the bacteria has been destroyed.

Journey Into the Unknown

"It tastes a bit like mushrooms," Tanja Diederen remarked as she took her morning phage dose. "When I went to Georgia, I was at first very nervous and excited, but above all disappointed about the treatment here in Holland."

After antibiotics stopped working for her, her doctor suggested that she take biopharmaceuticals, i.e. genetically engineered drugs. He had never heard of bacteriophages.

Instead, Diederen decided to look for treatment options with bacteriophages on her own, which she had heard about in a television program.

The Doctor Never Heard of Phages

A phage model — phages are viruses, that multiply in bacteria and then destroy them.

She came across the Georgi-Eliava Institute in Georgia, which has been researching bacteriophages since 1923 — just a few years after their discovery. Georgia has since developed into the global center of phage therapy.

During the Cold War, antibiotics were difficult to get there or anywhere in the Soviet Union. Treatment with phages was the best way to cure infectious diseases. Today, the Eliava Institute has one of the largest therapeutic collections of bacteriophages in the world.

Tanja Diederen stayed in treatment for two weeks, after which she traveled back to the Netherlands with a large suitcase full of phage tins. Since she began taking two different phages a day and applying a cream, she feels better.

She has more energy again and the small inflammations on her chest and armpits have decreased. The large inflammations come and go, but not as severe as before.

"It Doesn't Feel Illegal to Me"

Communicating with the Georgian doctors was difficult for Tanja Diederen. She needed a translator.

Every three months Diederen travels to Belgium — 15 kilometers away — to pick up a new ration of bacteriophages sent from Georgia for 500 euros. Her health insurance doesn't pay for this. Belgium is the only Western European country where phages are allowed. In the Netherlands, as in all other countries, they can only be used in individual cases to save lives or relieve severe pain.

Her physician is solely responsible for the application.

"It doesn't feel illegal to me," said Diederen. "I am one hundred percent sure that this medicine will help many people."

Like antibiotics, bacteriophages can also lead to bacterial resistance. Their big advantage, however, is that they are always one step ahead of the bacteria and can overcome the resistance. In addition, they are always directed against a specific type of bacteria and thus leave useful bacteria undamaged, like in the intestine, for example.

Before phage treatment, it is always necessary to determine which bacteria actually trigger the disease. The phages are then produced individually for each patient — often in Georgia.

Bacteriophages Permitted in Belgium

Professor Jean-Paul Pirnay from the Queen-Astrid Military Hospital in Brussels works with bacteriophages.

Such an individual medication does not meet the applicable regulations for medicinal products in any Western European country. It would take too much effort to have each individual phage formulation approved by the authorities.

Not so in Belgium. Since last year, this process can be legally circumvented by the Scientific Health Institute, in cooperation with doctors, patients, manufacturers, pharmacists and the Belgian Federal Office for Medicinal Products, issuing a certificate for the required phage ingredients. Pharmacists will then be able to use them for the manufacture of bacteriophages, subject to certain guidelines.

"We have used the existing legal framework to insert the bacteriophages," said Dr Jean-Paul Pirnay, who works at the Queen Astrid Military Hospital in Brussels on bacteriophages.

Around 30 patients have already been treated there. Currently, the military hospital is the only place in Belgium where bacteriophages are produced.

Useful Supplement to Antibiotics

"We need pharmaceutical companies to make the phage," says Pirnay. "A hospital can't produce all phages for a growing number of patients."

But industrial production of phages would require a clearer legal framework, and research is not yet ready.

"I believe that phages will not replace antibiotics," he said. "Both will be used together to make antibiotics more effective."

Tanja Diederen wants to continue her treatment in Brussels in the future. Communication with the Georgian doctors was difficult for her, she always needed a translator.

"I really hope that phages will soon be allowed in Europe," she said. "Going to Georgia is quite difficult and expensive."

Germany and the Netherlands are currently conducting pilot studies to see whether an individual prescription of bacteriophages would be possible. France has already imported Belgian phages and agreed to their use.

Reposted with permission from Deutsche Welle.

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Guillain-Barre syndrome occurs when the body's own immune system attacks and injures the nerves outside of the spinal cord or brain – the peripheral nervous system. Niq Steele / Getty Images

By Sherry H-Y. Chou, Aarti Sarwal and Neha S. Dangayach

The patient in the case report (let's call him Tom) was 54 and in good health. For two days in May, he felt unwell and was too weak to get out of bed. When his family finally brought him to the hospital, doctors found that he had a fever and signs of a severe infection, or sepsis. He tested positive for SARS-CoV-2, the virus that causes COVID-19 infection. In addition to symptoms of COVID-19, he was also too weak to move his legs.

When a neurologist examined him, Tom was diagnosed with Guillain-Barre Syndrome, an autoimmune disease that causes abnormal sensation and weakness due to delays in sending signals through the nerves. Usually reversible, in severe cases it can cause prolonged paralysis involving breathing muscles, require ventilator support and sometimes leave permanent neurological deficits. Early recognition by expert neurologists is key to proper treatment.

We are neurologists specializing in intensive care and leading studies related to neurological complications from COVID-19. Given the occurrence of Guillain-Barre Syndrome in prior pandemics with other corona viruses like SARS and MERS, we are investigating a possible link between Guillain-Barre Syndrome and COVID-19 and tracking published reports to see if there is any link between Guillain-Barre Syndrome and COVID-19.

Some patients may not seek timely medical care for neurological symptoms like prolonged headache, vision loss and new muscle weakness due to fear of getting exposed to virus in the emergency setting. People need to know that medical facilities have taken full precautions to protect patients. Seeking timely medical evaluation for neurological symptoms can help treat many of these diseases.

What Is Guillain-Barre Syndrome?

Guillain-Barre syndrome occurs when the body's own immune system attacks and injures the nerves outside of the spinal cord or brain – the peripheral nervous system. Most commonly, the injury involves the protective sheath, or myelin, that wraps nerves and is essential to nerve function.

Without the myelin sheath, signals that go through a nerve are slowed or lost, which causes the nerve to malfunction.

To diagnose Guillain-Barre Syndrome, neurologists perform a detailed neurological exam. Due to the nerve injury, patients often may have loss of reflexes on examination. Doctors often need to perform a lumbar puncture, otherwise known as spinal tap, to sample spinal fluid and look for signs of inflammation and abnormal antibodies.

Studies have shown that giving patients an infusion of antibodies derived from donated blood or plasma exchange – a process that cleans patients' blood of harmful antibodies - can speed up recovery. A very small subset of patients may need these therapies long-term.

The majority of Guillain-Barre Syndrome patients improve within a few weeks and eventually can make a full recovery. However, some patients with Guillain-Barre Syndrome have lingering symptoms including weakness and abnormal sensations in arms and/or legs; rarely patients may be bedridden or disabled long-term.

Guillain-Barre Syndrome and Pandemics

As the COVID-19 pandemic sweeps across the globe, many neurologic specialists have been on the lookout for potentially serious nervous system complications such as Guillain-Barre Syndrome.

Though Guillain-Barre Syndrome is rare, it is well known to emerge following bacterial infections, such as Campylobacter jejuni, a common cause of food poisoning, and a multitude of viral infections including the flu virus, Zika virus and other coronaviruses.

Studies showed an increase in Guillain-Barre Syndrome cases following the 2009 H1N1 flu pandemic, suggesting a possible connection. The presumed cause for this link is that the body's own immune response to fight the infection turns on itself and attacks the peripheral nerves. This is called an "autoimmune" condition. When a pandemic affects as many people as our current COVID-19 crisis, even a rare complication can become a significant public health problem. That is especially true for one that causes neurological dysfunction where the recovery takes a long time and may be incomplete.

The first reports of Guillain-Barre Syndrome in COVID-19 pandemic originated from Italy, Spain and China, where the pandemic surged before the U.S. crisis.

Though there is clear clinical suspicion that COVID-19 can lead to Guillain-Barre Syndrome, many important questions remain. What are the chances that someone gets Guillain-Barre Syndrome during or following a COVID-19 infection? Does Guillain-Barre Syndrome happen more often in those who have been infected with COVID-19 compared to other types of infections, such as the flu?

The only way to get answers is through a prospective study where doctors perform systematic surveillance and collect data on a large group of patients. There are ongoing large research consortia hard at work to figure out answers to these questions.

Understanding the Association Between COVID-19 and Guillain-Barre Syndrome

While large research studies are underway, overall it appears that Guillain-Barre Syndrome is a rare but serious phenomenon possibly linked to COVID-19. Given that more than 10.7 million cases have been reported for COVID-19, there have been 10 reported cases of COVID-19 patients with Guillain-Barre Syndrome so far – only two reported cases in the U.S., five in Italy, two cases in Iran and one from Wuhan, China.

It is certainly possible that there are other cases that have not been reported. The Global Consortium Study of Neurological Dysfunctions in COVID-19 is actively underway to find out how often neurological problems like Guillain-Barre Syndrome is seen in hospitalized COVID-19 patients. Also, just because Guillain-Barre Syndrome occurs in a patient diagnosed with COVID-19, that does not imply that it was caused by the virus; this still may be a coincident occurrence. More research is needed to understand how the two events are related.

Due to the pandemic and infection-containment considerations, diagnostic tests, such as a nerve conduction study that used to be routine for patients with suspected Guillain-Barre Syndrome, are more difficult to do. In both U.S. cases, the initial diagnosis and treatment were all based on clinical examination by a neurological experts rather than any tests. Both patients survived but with significant residual weakness at the time these case reports came out, but that is not uncommon for Guillain-Barre Syndrome patients. The road to recovery may sometimes be long, but many patients can make a full recovery with time.

Though the reported cases of Guillain-Barre Syndrome so far all have severe symptoms, this is not uncommon in a pandemic situation where the less sick patients may stay home and not present for medical care for fear of being exposed to the virus. This, plus the limited COVID-19 testing capability across the U.S., may skew our current detection of Guillain-Barre Syndrome cases toward the sicker patients who have to go to a hospital. In general, the majority of Guillain-Barre Syndrome patients do recover, given enough time. We do not yet know whether this is true for COVID-19-related cases at this stage of the pandemic. We and colleagues around the world are working around the clock to find answers to these critical questions.

Sherry H-Y. Chou is an Associate Professor of Critical Care Medicine, Neurology, and Neurosurgery, University of Pittsburgh.

Aarti Sarwal is an Associate Professor, Neurology, Wake Forest University.

Neha S. Dangayach is an Assistant Professor of Neurology and Neurosurgery, Icahn School of Medicine at Mount Sinai.

Disclosure statement: Sherry H-Y. Chou receives funding from The University of Pittsburgh Clinical Translational Science Institute (CTSI), the National Institute of Health, and the University of Pittsburgh School of Medicine Dean's Faculty Advancement Award. Sherry H-Y. Chou is a member of Board of Directors for the Neurocritical Care Society. Neha S. Dangayach receives funding from the Bee Foundation, the Friedman Brain Institute, the Neurocritical Care Society, InCHIP-UConn Center for mHealth and Social Media Seed Grant. She is faculty for emcrit.org and for AiSinai. Aarti Sarwal does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

Reposted with permission from The Conversation.