Capsid and Tail
A weekly phage periodical
May 30, 2019
Issue 30: Phage Therapy in India

Improving access to phage therapy in India

We interviewed Pranav Johri, a former phage therapy patient who founded Vitalis Phage Therapy to help others access phage therapy, especially in his home country of India.

This week’s article was co-produced with Kisaco Research, and can also be read on their site. While you’re there, don’t forget to download the agenda for their upcoming meeting, Phage Futures Europe, taking place in Brussels, Belgium September 25-26, 2019!

Sign up before early bird rates go up on June 15 and use discount code “PD10” for an additional 10% off.

Phage Futures Europe Banner

What’s New

This NPR article discusses Locus Biosciences’ upcoming E. coli urinary tract infection phage therapy trial and interviews one of the trial volunteers—Alfonso Evans, a US Army veteran who was paralyzed by a spinal cord injury and thus suffers frequent UTIs—and a physician involved in the trial, Dr. Michael Priebe of the Norwood VA Medical Center in Augusta, Georgia, USA. Starting later this year, volunteers will receive a cocktail of Locus’ CRISPR-engineered phages to test their safety.

Phage TherapyUTIClinical Trials

Diane Shader Smith is the mother of Mallory Smith, the 25-year-old who passed away in 2017 from an antibiotic resistant lung infection. Diane has given a TEDx talk (14 min) about Mallory’s life, legacy and memoir: Salt in My Soul. Diane describes their family’s efforts to promote and raise funds (so far $5 million+ for research, plus all Salt in My Soul profits to be donated) for cystic fibrosis and phage therapy, so they can save other lives.

Tedx TalkVideo

Two new phage bioinformatics tools for you this week: first, a phage host finding tool: link phages and potential hosts by finding shared attachment sites for prophage integration (GitHub), and second, Prophage Hunter: an integrative hunting tool for active prophages (Paper | Tool).

Bioinformatics Tool

A new patent on phage compositions and uses was published this month by Paul Turner, Benjamin Chan and John Wertz. Their invention includes phage compositions and methods to increase antibiotic sensitivity in bacteria, a pharmaceutical composition comprising a lytic phage, a method of treating multi-drug resistant bacteria, and a method of disrupting biofilms.

Phage Patent

This week on #PhageTwitter: a fantastic and informative Twitter thread (with images and videos!) by Patrick R. Secor (@PRSecor) on how filamentous P. aeruginosa phage Pf spontaneously forms liquid crystals in the presence of polymers, which contributes to antibiotic-resistant biofilm formation by its host.

#BestOfPhageTwitter

Latest Jobs

Senior Scientist - Phages
PhagoMed Biopharma GmbH, Vienna, Austria
Dr. Lorenzo Corsini

Do you want to be part of pioneering a high-profile antibiotics alternative and lead the research into breakthrough phage applications in areas of high medical need – together with a highly talented team and a network of leading physicians? Then apply for PhagoMed’s current vacancy as Senior Scientist - Phages.

Role description:

  • Establish research processes according to the latest microbiological technology developments (e.g. robotics and genomic data);
  • Further establish and validate potency model for phages against bacteria in biofilm models and planktonic growth;
  • Analyze the effect of phages on bacteria, including MIC, time-kill curves and other relevant parameters for antimicrobials, resistance formation, in planktonic growth and on biofilms
  • Further develop the PhagoMed phage breeding protocols to enhance selected properties of our target phages, e.g. lytic activity in biofilm and pharmacokinetics;
  • Evaluate immune response to phages;
    […]
Senior Scientist Phage Therapy
Junior Researcher
PhagoMed Biopharma GmbH, Vienna, Austria
Dr. Lorenzo Corsini

Do you want to be part of developing a high-profile antibiotics alternative and help drive the research into new phage-based pharmaceuticals – together with an experienced and motivated team and a network of leading physicians? Then apply for PhagoMed’s current vacancy as Junior Researcher.

Role description:

  • Execute series of experiments to support the developmental program, all following established protocols, including:
  • Production and purification of bacteriophages for scientific research
  • Activity testing of phages against bacterial strains (BSL-2 strains like S. aureus, E. coli, other)
  • Selective breeding of phages
  • Host range analyses
  • Biofilm assays
  • Isolation of bacteriophages from human and environmental samples
  • Characterization of bacteriophages (adsorption rate, latency period, burst size)
    […]
Junior Researcher Phage Therapy

Community Board

May 30, 2019
Register now for the 2019 Evergreen Phage Bioinformatics Workshop
Name: Betty Kutter & Evergreen Organizers
Location: Olympia, WA
Organization: Evergreen International Phage Meeting

The 2019 Evergreen Phage Bioinformatics Workshop will consist of three tracks: Genomics with Galaxy & WebApollo; Genomic annotation with PATRIC; and Viromics (metaviromics). Participants are invited to register for one of these tracks on Saturday (4 PM – 9PM, 4h of work, with a break for supper), and/or for one of these as repeated on Sunday (8:30 to- 12:00, 3 ½ h). Each track will consist of an introductory lecture followed by hands-on sessions where participants can work on example datasets.

Observers are also welcome in each of the 3 sessions. (Note: Participants need to work on their own laptops; no computers will be provided.

We will plan on having a van pool for people arriving Saturday morning. For people taking part in the Saturday workshop, there will be an extra $10 fee from Evergreen for using their facilities.

The 3 tracks are:

  1. Genomics – Annotation: with PATRIC (Ramy Aziz & PATRIC people): Phage annotation using RAST and PATRIC. This track is suitable for beginners.

  2. Genomics - Phage genomics: with Galaxy and WebApollo (Jason Gill): This track will cover the start-to-finish process of whole-phage genomics, including DNA sequencing, assembly, end determination, annotation, and comparative genomics using the user-friendly interfaces Galaxy and WebApollo. This is suitable for both beginner and intermediate users. There will be a limited number of participants for people doing their own genomes, but the 2 hour lecture is open to all, the hand-on portion can handle about 15 people working on their own genomes.

  3. Viromics – (Alejandro Reyes & Evelien Adriaenssens): introduction to sequence pre-processing, clean-up, and assembly using command-line tools; visualization of data. Suitable for users who know how to navigate a command-line environment.

Register here for the Genome Workshops!

And if you haven’t yet registered for the Evergreen phage conference itself (Aug 4-9), register here!

Workshop GenomicsViromics
May 30, 2019
Seeking soil samples for phage isolation
Location: College Station, Texas
Organization: Center for Phage Technology

Howdy phage enthusiasts! The Center for Phage Technology is currently seeking out new environmental soil and water samples for phage isolation! Direct message the CPT on Twitter if there’s something you’d like to send! We’ll cover shipping and can even send you a kit to get started! #phage #science #savingtheworld #CitizenScience

Request for participation Phage Isolation

Improving access to phage therapy in India

Jessica Sacher, PhD
LinkedIn | Twitter

Pranav Johri founded Vitalis Phage Therapy in 2017, which partners with the Eliava Phage Therapy Center to help people get phage therapy when antibiotics fail.

We interviewed Pranav about how and why he got started, and provide a deep dive into his personal story. We follow this with a Q & A about what his organization does, how it’s been received to date, and what his team’s goals are for the near future.

This week’s article was co-produced with Kisaco Research (and can also be read on their site), in support of their upcoming conference, Phage Futures Europe (see the agenda or register here — use discount code “PD10” for another 10% off)

Pranav’s personal experience as a phage therapy patient

An infection that wouldn’t go away

Pranav didn’t learn about phages or phage therapy until a couple of years ago. His story starts in 2015, in his early thirties, when he was dealing with a five-month long recurrent respiratory infection. He would take antibiotics, it would go away for a while, and then return a few weeks later.

Eventually, one of the courses of antibiotics took away his respiratory symptoms, but then pains in his pelvic region began. This was new. He thought it might be muscular, thought it would settle down, but it didn’t. After a month, he was referred to a urologist, who diagnosed him with prostatitis (inflammation of the prostate gland, which can be caused by bacterial infection). This led to another series of antibiotic treatments: first one course, then two, then three. All different classes of antibiotics. No improvement of symptoms, and eventually, symptoms started to worsen.

Told to go home and “manage symptoms”

Eventually, a referral to a more senior urologist. Finally, some tests to identify the pathogen, but they showed nothing. Still, the new doctor prescribed more antibiotics: a combination of two. A “heavy artillery” given intravenously. And yet symptoms still worsened, including a low-grade fever that had now been persisting for months. After 5 courses of antibiotics, the doctor finally said “we have tried all the antibiotics we could for your condition, we really don’t know how to help you now”. Pranav says this was like running into a brick wall. “You always expect medical science to have answers for you.” The doctor said he should try to manage his symptoms with diet, exercise and rest. “How do you expect me to live with a fever?” The doctor said to schedule frequent nap times.

Unacceptable news

For Pranav, this was unacceptable. By this time, he had started discussions with urologists specializing in dealing with prostatitis. One of them suggested getting his prostate fluid and semen samples tested. He could not find a urologist locally to do a prostate fluid test, but his semen culture revealed two bacterial genera colonizing the prostate: Staphylococcus and Enterococcus. Both were resistant to many of the antibiotics Pranav had already taken.

The search for an alternative

During this time, Pranav had started researching what to do when antibiotics don’t work. This is when he came across phage therapy. Fortunately, Pranav was able to get help from his uncle, a molecular biologist, to validate some of his research findings. His uncle referred him to some phage scientists around the world. He was directed to the Center for Phage Technology at Texas A&M University, MIT, and the Pasteur Institute in Paris. They were helpful, and gave their opinion on phage therapy and the various places that practice it. In these conversations, the Eliava Phage Therapy Center in Tbilisi, Georgia and the Phage Therapy Unit in Wroclaw, Poland kept coming up. Pranav opened dialogue with both places. Eventually, he and his wife, Apurva, became confident and convinced enough in the validity of phage therapy to try it.

The decision to try phages

It was around this time that Pranav found out the results of his testing: resistant to all antibiotics he’d tried, and to the few remaining antibiotics his doctors would have tried next. “Seeing those reports pretty much closed the door on antibiotics, and by then I felt more convinced about phage therapy”, recounts Pranav. Thus began another month in heavy communication with phage experts, and in November 2016, Pranav travelled to Tbilisi, to the Eliava Phage Therapy Centre, for phage treatment.

Phage treatment at the Eliava

The first week at Eliava involved diagnostic testing, and the results showed the presence of four different species of bacteria: Staphylococcus aureus, Enterococcus faecalis, Staphylococcus haemolyticus, and Streptococcus mitis. The tests confirmed the antibiotic resistance patterns, but luckily, most of his infections appeared sensitive to the standard phage cocktails that Eliava makes.

Pranav’s treatment started Nov 23, 2016, coincidentally on his wedding anniversary. Four days after starting the phages, he started feeling better. “Not all the way better, but there was improvement.” First, the low-grade fever he’d had since July of that year finally went away around the 4th day: “a big breakthrough”, he says.

Gradually, he started seeing improvement in his other symptoms. Three weeks after arriving in Tbilisi, they repeated diagnostic testing and found that one of his bacteria, the S. aureus, was completely eliminated. Two of the other strains were reduced in numbers, but the Streptococcus mitis was resistant to all of Eliava’s standard phages. The Eliava doctors suggested putting the latter aside and focusing first on the phage-sensitive strains.

On the right track

By December 10th, with Pranav feeling about 25% better, and with one bacterial species gone, he was told he could return to India and continue taking the phages there. In January 2017, Pranav went back to work, and by the beginning of March, he’d completed the full course of phages he’d taken home. He was feeling about 50% better: “I felt like I was on the right track”. He provided fresh samples to the Eliava Institute again, and the results showed that both Staph species had been eliminated. E. faecalis was down in number from 10^9 CFU/mL to 10^4 CFU/mL, a marked improvement. However, the Strep remained as-is: resistant to all standard phages. At this point, the Eliava doctors suggested starting another phage course for the E. faecalis, followed by local diagnostic testing back home in Delhi. The plan was that if the Strep remained after that point, they would prepare a custom phage preparation to target his strain.

By summer 2017, Pranav had finished the phage and been re-tested. The E. faecalis was gone, so now only the Strep was left.

Helping others access phage therapy

Back when Pranav was doing his research into antibiotic alternatives, he came across many others dealing with similar struggles. Lung infections, UTIs, respiratory infections, prostate infections: none responding to antibiotics. During the time Pranav was getting phage therapy, he shared his treatment experience with many of these people. As he started feeling better, he realized that phage therapy needed to be made known more widely as an option: “It shouldn’t be something that only someone with resources like I had available can take on. I had people in my family who could put me in touch with scientists around the world to validate my research. I run a successful publishing company, so I had enough financial resources to travel to another country and receive treatment. Not everyone has these resources, and I felt that an enabling infrastructure needed to be created to make phage therapy accessible to more people.”

At this point, Pranav began a discussion with the management of the Eliava Phage Therapy Center about his desire to make phage therapy more accessible, especially for people in his home country of India. They were open to the idea, liked the sentiment, and asked him what he had in mind. Encouraged, Pranav started brainstorming. “In publishing I had a lot of media contacts. I thought I could start by making a buzz in the media. Media paints antibiotic resistance as a problem, but a solution is never proposed. I said let’s start changing that narrative, let’s talk to health editors, and make people aware of this option.”

Identifying the barriers to phage treatment

As Pranav started to get the word out about his story, and communicating with more and more people, he started coming across logistical problems. For example, it was difficult to send samples from India to Georgia, and difficult for phages to be shipped to India because of customs. To begin to overcome these hurdles and enable easier access to phage therapy, Pranav and his wife Apurva created a structure called Vitalis Phage Therapy. Discussions with the international patient coordinator at the Eliava Phage Therapy Center, Dr Naomi Hoyle, and with FedEx and DHL in India, revealed how samples could be sent from one country to another in a way that was acceptable to shipping companies and customs. Through these discussions, they learned about special kits for shipping biological samples like urine and sputum. They imported kits from the US and started making them available to people in India.

Formalizing a partnership with Eliava

In November 2017, at which point all but one of Pranav’s bacterial infections had been eradicated, Pranav returned to Eliava for two reasons: to get treatment for his Strep infection (they’d prepared a custom phage) and to formalize a partnership with Eliava. By this time, other patients of Eliava who’d had positive phage therapy experiences also wanted to make treatment available in their own countries, so Eliava had started setting up a network of partners.

Media buzz

By early 2018, Pranav and the Vitalis team had figured some of the logistical issues they’d encountered. They also had started meeting with health news editors, who started showing interest in Pranav’s story. “They’d ask, ‘you had the option of going anywhere in the world, and you went to Georgia. Why?’,” says Pranav, “They’d also ask about how I got enough confidence to try phage therapy.” He would respond by telling them, “Even in the most advanced countries, doctors were only able to offer me antibiotics. I had already tried those and they failed in treating me. Georgia is one of the only places that had a credible alternative solution to my problem.”

Initially, the media focused just on Pranav’s story, but gradually this changed: “They started asking us more about the number of people that had been helped with phage therapy, the conditions that had been treated, and the logistical barriers we were trying to remove,” remembers Pranav.

A new barrier: a patient too sick to travel

In August 2018, Pranav was contacted by a lady whose father had a hospital-acquired kidney and bladder infection. He was not in a condition to travel. She asked Pranav whether they could enable distance treatment for him. “This was the first person from India we came across who required phage treatment but could not travel”, says Pranav. This led them to work closely with Eliava to set up the infrastructure to enable distance treatment using Eliava’s phages in India. This ended up widening the number of people who were able to take the treatment. Number one, it reduced costs, and number two, people too sick to travel could still be treated.

Another barrier: phage diagnostics too slow for some patients

From September 2018 to the present day, Pranav says they’ve had a lot more people in India taking distance treatment. But still, distance treatment can mean waiting three weeks for samples to get from India to Georgia, and for reports to come back. This is too long for some patients.

In response to this problem, Vitalis Phage Therapy is now working to set up phage diagnostic testing capacities in the big cities of India, starting with Delhi. The phages would come from Eliava, and phage diagnostic services would be available locally in India. Reports on phage sensitivity testing could take as little as four days instead of three weeks. “That means phage therapy can be possible for a lot of people who can’t wait”, says Pranav.

Present day: Pranav’s health is restored, and Vitalis making a difference

These barriers and Vitalis’ response to them share a common thread: first, find out the issues people are having, then find solutions to those issues. “We’ve been trying to spread the word, and as people contact us, find out what they really want. For example, distance treatment came up when we found someone who couldn’t travel. And acute cases led us to try to make diagnostics more accessible.”

In the meantime, Pranav’s own test results showed that he was finally cleared of his infection. As of now, he’s been symptom-free for a year.

Q&A with Pranav

This interview has been lightly edited for clarity.

What’s been the public’s response to hearing about Vitalis and phage therapy?

When we started talking about how phages are a way to combat AMR infections, a lot of people came forward and said “I’m dealing with an infection now for 5 years”, or “My mother’s had an infection for 3 years,” and, “we were told we had no options left because the bacteria are antibiotic resistant”. For a lot of people, it’s an eye-opener that there actually is a treatment option when you have an antibiotic resistant infection. It’s not the end of the road. It was inspiring to see these people come out. They had given up hope.

Are patients generally happy with the treatment they receive?

Many of these people took phage therapy and are doing much better now. Some are completely fine, have gone back to their lives and work. Some are about 70% better, their infections contained to an extent. It’s great to see their experiences, and it’s given me a lot of confidence to go out and talk about it with more vigour. It’s not just my story anymore. We have more than 25 people now from India who’ve taken phage therapy in the past 10 months for a variety of infections: respiratory, bladder, wound. We’ve seen a more or less broadly positive outcome. It’s giving people more confidence, as it’s no longer just one anecdote.

What’s been the response from doctors in India?

Initially, the doctors were not very positive about this. They would question the origin of this treatment. Most of the doctors I consulted studied in the US, Canada or Western Europe, so their mindset is very set in a Western framework of medicine. So instead of me trying to convince them with my personal story, I decided to talk to a wider audience, let the people know about phage therapy as an option, so whoever wants to partake has that option. Now as the narrative around phage therapy is strengthening, we are getting inquiries from doctors. This Friday I am presenting to a team of 25 senior doctors and hospital administrators about phage therapy, starting with my personal experience and then about the wider perspective of what we’ve been doing. So we’re seeing a change in their mindset.

Can you tell us about the phage therapy research landscape in India?

Labs doing research with phages in India usually tend to be university labs. They’re isolating phages, trying them in animal models, and some of these labs have phage libraries they’ve been able to create against common bacterial infections like E. coli and Pseudomonas. There are many phage scientists in India willing to talk about how phages work, their scientific origin, how if they’re isolated and purified properly, they can be safe for human use.

How have phage scientists responded to what you’re doing?

Phage scientists in India were the first people who gave us a big thumbs up, the first who cheered us on when we launched our website. Within the first week of launch, we had a number of phage scientists who’d tweeted about our site, shared it on social media, saying it was so good to see someone with a positive experience with phage therapy coming out and talking about it and wanting to make the treatment accessible to others. They knew of phage from a scientific perspective, but I was the first human story of someone close to them that they’d heard of. One scientist from Delhi called me and said “I’m coming to your house, please take a few hours to meet me, tell me your whole story”.

Do people from other countries approach you?

Yes. Our infrastructure is mainly focused on India, but we do get contacted by a lot of people from around the world. People have the same questions I had. I’m able to relate closely to their anxieties, worries and doubts. I had all of those same ones when I went in for phage therapy. We didn’t expect initially to hear from people outside India, but it’s very good to hear from them and be able to help them access phage therapy. Antibiotic Resistance is a global problem.

Does Indian regulation control who can get phage therapy?

When we were looking at starting a partnership with Eliava, we had our legal team do research into Indian regulations around phage therapy. Interestingly, phages are mentioned in the Indian Drugs and Cosmetics Act. The act mentions them, acknowledges phages, but is quiet about them. The regulatory environment in India is fairly open to alternative forms of medicine. For example, Ayurvedic medicine originated in India, and the regulations allow it. Within the confines of personal medicine, regulations don’t bar alternative medicine. We found the same thing when we met with customs representatives. They said if medicine is imported for personal use directly by the person who will take the medicine, that’s allowed. They told us what documentation was required for shipping, which Eliava was already preparing for shipping phages to other countries.

Can you tell us more about the phage diagnostics testing you’re setting up in India?

India has a fairly robust diagnostic lab testing infrastructure across the country, but currently, the bacterial culture reports only show antibiotic sensitivity and not phage sensitivity. If these reports were to include phages, treatment could start much faster. We’re in the process of creating a legal and administrative framework to enable this within the next few months. It’s never been done before. We need to make sure Eliava’s phages are protected, and only used for the purpose of diagnostic testing.

Do patients pay for your services?

We don’t charge patients for what we do. This is something we are doing to improve access. The patients only have to pay the cost of treatment at Eliava. India is a generally low-income country so this cost is steep for a lot of people. Even for the kits we import for people to send samples to Eliava for testing, we just ask people to reimburse their cost, we don’t sell them.

What are your next steps?

We’re seeing a greater number of people contact us every month through media articles and our website. Right now we’re using the obstacles they face to guide our next steps. When we saw a travel constraint, we enabled distance treatment. Sending samples to Georgia for testing takes time, so we are trying to set up diagnostic lab testing with phages in India. The next barrier that we will be trying to solve is affordability of the treatment for people who need it but for whom the costs are too steep.

What would help you most at this point?

What helps us going forward is getting the message out to more people, more media, more health editors, and to doctors, and connecting with people doing similar things. Many of us are working in silos, and if we could all come together and share experiences, knowledge, and best practices, that would help. In general, the more connected we can all become in this ecosystem, the better.

The scale of the antibiotic resistance problem is mind boggling, especially in India. India is the largest consumer of antibiotics in the world. We consumed 13 billion tablets of oral antibiotics in 2017. The problem of resistance is very, very prevalent here. It is severe. The more outreach that could be done, around phage therapy, making it accessible, showing people how they could benefit through infrastructure and personal experiences, those kinds of things would really help going forward.

Jessica Sacher, PhD

LinkedIn | Twitter

Jessica Sacher is a co-founder of Phage Directory and has a Ph.D in Microbiology and Biotechnology

For every issue of Capsid & Tail, we are committed to getting our facts straight, but we’re not experts in the information we’re bringing to you. If you feel that we’ve missed an important viewpoint, or if you have something to add, please reach out to us by emailing [email protected]. We’d love to hear from you, and we’d be happy to revisit topics we’ve covered (ideally with added information and viewpoints from community members like you!).

Lastly, please reach out if you’re interested in writing for us, or have suggestions for future issues!