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What is antimicrobial resistance (AMR) and why you should know about it

Pharmacist holding medicine box and capsule pack in pharmacy drugstore.

 

Today marks the beginning of World Antimicrobial Awareness Week, driven by the World Health Organisation to improve global knowledge of antibiotic drugs. Running from the 18th to the 24th of November, the awareness initiative is focused on uniting to preserve effective antimicrobials and reduce or prevent the spread of Antimicrobial Resistance (AMR), which is becoming an increasing concern across the world.

Before we jump deeper into the AMR and the global impact it will have if not addressed, let’s briefly cover the history of antimicrobials in medicine. 

1910, the first breakthrough in antimicrobial treatment

These life-saving drugs are rather ironically named, since the literal meaning of antibiotic is ‘anti-life’ or ‘against living’ – but in this case, the living organisms that produce the disease’. 

Selman Waksman first used the term ‘antibiotic’ during the 1940s. Until then, antibiotic drugs were simply referred to by their names. 

While there are anecdotal accounts of antimicrobial treatments being administered during ancient times, the breakthrough moment was the creation of the first synthetic antimicrobial agents by Paul Ehrlich who noted that certain dyes would color bacterial cells but not others.

Ehrlich thought that if these cells could be isolated, and that selective chemicals could be used to target and neutralize bacteria. 

Ehrlich worked with the toxic element arsenic to produce compound 606, which was introduced in ca. 1910, under the name Salvarsan. Salvarsan, now known as arsphenamine, was the ‘drug of choice’ to treat syphilis until the 1940s.

1928, Fleming discovers penicillin

Treatment of syphilis with Salvarsan was superseded by the most famous antibiotic of them all – penicillin. This antibiotic is derived from natural substances, in contrast to dyes and arsenic derivatives. Early observations of penicillin properties were made by William Roberts and Louis Pasteur during the close of the 19th century however,  it was not until 1928 that a revolutionary discovery was made by Sir Alexander Fleming, who was studying a green mold (Penicillium chrysogenum) in his laboratory. 

Fleming discovered that the mold killed and prevented the growth of bacteria. He deduced that the mold must be creating a specific substance, and he named this ‘mold juice’ penicillin. 

This first antibiotic was not isolated and purified until 1942, by two Oxford scientists Ernst Chain and Howard Florey – who shared the 1945 Noble Prize in Medicine with Fleming.

In the following decades, at least a dozen additional antibiotics entered the medical field, creating an arsenal for use against several major diseases.

2020, emerging antimicrobial resistance (AMR)

What is AMR? AMR stands for “antimicrobial resistance” – a process of pathogen adaptation, whereby bacteria, viruses, fungi, and parasites develop defenses that make antimicrobials less and less effective. Ultimately, treatment times are prolonged,  increases the risk of spreading disease, and developing complications. 

When a tried and proven medicine is no longer effective at fighting its targeted disease, an alternative is needed, which might take years to develop. A “worst-case scenario”  will result, in which pathogens ‘outsmart’ humans, and we are left without drugs needed to cure even the most common bacterial infections.

Why is this happening? The misuse and overuse of antimicrobials, including instances of viral diseases (where they are ineffective) have allowed pathogens to be exposed to more and more medicine, encouraging the selection of strains that have lost their susceptibility to these compounds. 

Issues such as poor water quality, lack of sanitation, and substandard hygiene have also hastened the spread of antibiotic-resistant infections. 

It is up to us all to recognize AMR as an emerging global health threat, act to prevent and treat the infection using properly targeted drugs at the proper dosage and duration of therapy.

 

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From the desert to the lab: Dr. Berger

Today is the birthday of our co-founder Dr. Stephen A. Berger, and the perfect time to share his personal story and the history behind the creation of GIDEON.

Steve has been the “beating heart” of the company’s medical knowledge and insight since its inception. GIDEON could not be what it is today and will be tomorrow, without him. Join us on Memory Lane as we celebrate Dr. Berger’s contribution to the medical community.

A TALENTED YOUNG DOCTOR

Steve was brought up in New York and was destined to become either a lawyer or a doctor. Thankfully for us, he fell in love with the latter field. Dr. Berger graduated with a medical degree from the New York Medical College in 1967 and completed his Internal Medicine training there as the youngest in his group, finishing at the top of his class too! 

After this, the Vietnam war erupted, and along with many junior doctors, Steve was conscripted into the US Navy. Despite not being well-traveled at the time, he took this in his stride and developed an interest in Infectious Diseases – something that set him apart from his peers back in New York.

He was assigned to the Sixth Fleet, stationed in the Mediterranean, which eventually took him to Israel. At the time, Dr. Berger explored his Jewish roots, and this is where he eventually made his home.  

LT Steve Berger, U.S. Navy
LT Steve Berger, U.S. Navy

 

After emigrating, Steve found the love of his life – an accomplished medical professional in her own right and currently Israel’s leading pediatric surgeon, as well as the first Yemenite to graduate medical school in Israel. 

While in the country, the Yom Kippur war broke out (1973). This is when this second photo was taken – next to the Suez Canal…and on his birthday!

Dr. Steve Berger, Suez Canal
Dr. Steve Berger, Suez Canal

 

DOUBLE CERTIFIED

The lady who captured Dr. Berger’s heart in Israel was on her way to train in the United States, and so Steve returned to continue his education in New York. 

This is where he completed Infectious Disease fellowships at Montefiore Hospital-Einstein in New York, The New York V.A. Hospital, and the Tufts-New England Medical Center. Here, he got to work with Dr. Louis Weinstein,  “a leading pioneer in the new specialty of Infectious Disease”. Dr. Weinstein was Steve’s Guru and mentor and for all that followed in his career.

To supplement and expand his knowledge base, Dr. Berger went on to train in Clinical Microbiology eventually attaining Board Certification and Licensure in both Israel and the United States – in the fields of Internal Medicine, Infectious Diseases, and Clinical Microbiology. 

During this period, Steve established clinical and teaching programs at the New York Medical College, and was granted the rank of Associate Professor. Dr. Berger then returned to Israel, where he established the country’s first automated Microbiology Laboratory, at the central municipal hospital in Tel Aviv; and devoted endless energy to teaching and research as Associate Professor of Medicine and Microbiology at Tel Aviv University. 

DISCOVERING BAYES

In 1987, Dr. Berger was sent to Brussels for advanced training under the World Health Organization in Operational Methods. Much of this program involved drawn-out discussions of how to organize medical services in primitive environments and hands-on experience with practical statistical methods. In one such session, Steve first came aware of Bayesian analysis.  Intrigued, he asked the presenter if anyone was using the method in diagnosing disease.  Apparently, the tool was largely unknown in the field of Medicine! 

Upon returning to Israel, Dr. Berger began running Bayesian diagnosis simulations but was forced to struggle with the limits of available computer technology.   It was then he met Uri Blackman, the other half of the GIDEON team.

Bayesian Theorem
Bayes’ Theorem

THE BIRTH OF GIDEON

Dr. Berger’s medical and scientific expertise  – combined with Uri’s technical and business acumen  – gave life to the first prototype of GIDEON.  The very first hand-on test involved a “real-life” patient with typhoid fever. Much to Dr. Berger’s and Uri’s joy, GIDEON worked perfectly!

The next three years were focused on gathering as much background data as possible for the world’s most comprehensive Infectious Diseases database. 

In the early days, data were gathered and added to the system manually, from “actual” books and journals.  The Internet has still not been developed. The first version of GIDEON was marketed on floppy discs, mailed quarterly to subscribers (later to be replaced by Compact Discs which incorporated advanced computer programming capability).  Nowadays, GIDEON is updated daily over the Internet and incorporates information from dozens of digital sources worldwide. 

The GIDEON database was later reverse-engineered through a system in which databases are “turned back” into books.  As of 2020, 430 e-books (120,000 single-space pages) present the entire field of Infectious Diseases, with individual titles devoted to every country and every disease. An updated edition of all books is released yearly. 

A WARM RECEPTION

The medical community immediately fell in love with GIDEON.  A number of medical institutions and physicians have continued to subscribe to the program from the very first launch in 1993.

Dr. Berger recalls an event when one enthusiastic Texan shouted, “Wow, this is better than sex!”’ at a medical convention, after seeing a correct diagnosis appear on the computer screen.  Owing to a warm reception of the Diagnosis module, the development of a new Microbiology module soon followed.  For years, an increasing base of users has signed on from all over the world – taking advantage of GIDEON’s unique knowledge base, and tools for research teaching, diagnosis, and pathogen identification.  

Dr. Berger is most proud of GIDEON’s achievements when hearing from scientists and students who have used the resource to fuel new ideas or solidify tried and tested principles.  

ACCOMPLISHED LIFE

All the while, with GIDEON going from strength to strength, Steve and his wife raised three children, and now enjoy five grandchildren, while continuing to pursue their medical careers. 

Dr. Berger opened the first Travel Medicine clinic in Israel and is currently Director of Geographic Medicine at the Tel Aviv Medical Center.  He has published 11 standard texts and 180 professional papers (in English and Hebrew) –  in addition to the hundreds of eBooks available through GIDEON.

In his spare time, Steve enjoys classical music (Schubert and Bach in particular) and science fiction (anything by Isaac Asimov). He also maintains an interactive database that catalogs the world’s largest “collection” of diseases and deaths among famous people – currently exceeding 23,000 people. Check it out at VIPatients – truly fascinating! 

 

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COVID-19 and Fame

Ask anybody on the planet, “What do Tom Hanks, Boris Johnson, and Prince Charles have in common?” and they will instantly shout – “Corona.”

Ask these same people, “Who were the three Prime Ministers that died of Coronavirus last month?” Few will respond, “Well…there was Nur Hassan Husein from Somalia, Mahmoud Jabril from Libya and Joachim Yhombi-Opango from Congo – who died (respectively) in London, Cairo, and Paris.”

As of May 4, no fewer than eleven movie stars had contracted COVID-19, nine with fatal results. Other victims include retired Commanders of the Turkish and Polish Armies, a well-known rapper, and a mafia hitman. Almost half of the famous COVID-19 victims have been athletes, not surprisingly from countries that report unusually high rates of infection (see list below).

History is largely written in the lives of famous disease victims. The “black death” of 1348 claimed only eleven well-known people, including the King of Spain, the Royal Consorts of England and France, four famous painters, and two Archbishops of Canterbury. In contrast, 62 famous people died during the “Spanish Influenza” pandemic, accounting for 39% of known causes of death in this population from 1918 to 1920!

COVID-19 in Athletes

  – fatal
  – soccer
– American football
– basketball
– cricket

Argentina

Ezequiel Garay 

Brazil

 Jonathas de Jesus

Denmark

 Thomas Kahlenberg

 Peter Madsen

England

 Callum Hudson-Odoi

 Norman Hunter 

 John Rowlands 

France

 Eliaquim Mangala

 Arnold Sowinski 

Gambia

 Omar Colley

Germany

 Jannes Horn

 Timo Hubers

 Luca Kilian

 Fabian Nurnberger

 Stefan Thesker

Italy

 Zaccaria Cometti 

 Fabio Depaoli

 Innocezo Donina

 Alessandro Favelli

 Luciano Federici 

 Manolo Gabbiadini

 Antonino La Gumina

 Daniele Rugani

 King Udoh

Netherlands

 Henk Overgoor

Norway

 Morten Thorsby

Pakistan

 Zafar Sarfraz   

Poland

 Bartosz Bereszynski

Serbia

 Dusan Vlahovic

Somalia

 Mohammed Farah

South Korea

 Hyun-jun Suk

Spain

 Baldiri Alavedra

 Mikel Arteta

 Goyo Benito

 Jose Luis Capon

 Jose Luis Gaya

 Benito Joanet

 Miguel Jones

Sweden

 Albin Ekdal

United States

 Tom Dempsey

 Rudy Gobert

 Orlando McDaniel

 Donoval Mitchell

 Christian Wood

Don’t panic. Prepare

Dr.Tracey McNamara on West Nile Fever and COVID-19

 

As interviewed by Edward Borton, GIDEON

What was the experience of discovering a new virus outbreak on your doorstep?

When New York City announced that people were dying of unusual encephalitis, I was struck by the timing and proximity between this event and an outbreak of crow deaths. Upon ruling out all known viruses that cause inflammation of the brain in birds, in the United States: exotic Newcastle, avian influenza, and Eastern Equine encephalitis (EEE), I knew this was something new.

It wasn’t until I picked up the phone and called the U.S. Army and said “I think it’s something new to veterinary medicine. I think it’s the same thing killing people in New York City, but no one will test my samples.” That one phone call changed everything because the military had a different mindset. When you say ‘something unusual, new and killing people’, they immediately thought of bioterrorism, and the West Nile virus is indeed a biowarfare weapon.

 

Was there a significant media response at the time? How does the response compare with what we’re experiencing today?

It was pretty crazy. We faced the same situation: a disease that we had never seen in the Western Hemisphere, and knew nothing about. We didn’t know what it was going to do, who it was going to make sick, only that it had already killed people. The scientists had nothing but questions about this virus and the public was extremely anxious.

To minimize panic, everyone was told ‘it’s only affecting the very young and the very old’.  Public health officials were telling people to wear mosquito repellent and destroy mosquito habitats if found in or near your home. Sadly, a lot of people were saying, ‘I don’t have to worry about this’.

It seems to be an instinctive response to a novel threat, to just deny it,  but sticking your head in the sand doesn’t mean something isn’t going to walk up and bite you on the butt.

 

Do you feel that the technology available to the industry is sufficient right now or does it need to improve before we start moving things forward?

I think the technology is there. There are companies using artificial intelligence and algorithms to detect anomalous events. It just hasn’t been applied to the animal sector.

We need to improve the speed of diagnostics. When the Ebola virus outbreaks took place, that prompted scientists to look into portable deep sequencing in the field. There is a company that developed a tool that’s smaller than a lunchbox, which allows you to take a swab, stick it in the device and in two hours you can download the results to your laptop. In two hours, you could know what you’re dealing with, whether it’s Ebola, or another virus, bacteria, fungus, parasite or unicellular organisms.

Another really powerful thing is a species neutral diagnostic test. It doesn’t matter if it’s human, environmental or animal. We’re probably talking 10 years from now, but it has been deployed in the field for Ebola, so we will eventually replace all our other methods of diagnostic tests we’re currently using.

 

Do you think we’ll see a new wave of people inspired to get involved in healthcare as a result of the current outbreak? 

Yes, I think so. Young people, they’re so interconnected, they’re online constantly. They will make terrific advances.

There is a phrase used when teaching medical students – ‘when you hear hoofbeats in the distance, think horses, not zebras.’ None of us can afford to think that way anymore, we all have to be thinking about zebras.

We, as human beings, have to find a way to bring all of our expertise together and to respond quickly. That will prevent major mortalities, no matter what profession you’re in. We all have a different mindset but that is what we need – multi-disciplinary teams.

We truly are all in this together and everyone has a role to play. I hope everyone keeps that in mind. Don’t panic. Prepare. Don’t get scared. Prepare. Work with the officials that are working around the clock trying to get their arms around us.

 

Dr. Tracey McNamara was hugely influential in the discovery of the West Nile Virus outbreak in the United States in 1999 and has been in the field of veterinary pathology for over 32 years, including Professor of Pathology at Western University of Health Sciences for almost 13 years.

Tracey gave a TedX talk at UCLA on ‘How monitoring animal health can predict human disease outbreaks’, which is available here.

 

Is COVID-19 the new plague?

written by Dr. Stephen A. Berger

Illustration of plague outbreaksA frightening pandemic arises from animals in Asia and spreads westward, killing thousands in Italy, France, Spain, and many other countries. The more severe infections are characterized by cough and fever, leading to progressive pneumonia. There is no specific treatment available, and entire cultures live in fear and uncertainty.  

And so, during 541-542 C.E. Yersinia pestis the bacterium that causes bubonic plague, spread out from China into the Byzantine Empire. Few were spared, and an estimated 25 to 100 million Europeans went on to die during repeated waves of infection that struck the region over the next 200 years. As many as 5,000 plague deaths per day were recorded in the city of Constantinople. This “Justinian Plague” is named for the Emperor Justinian, who managed to survive an attack of the illness (less-fortunate victims included Pope Pelagius II and Wighard, Archbishop of Canterbury) 

In recent years, much is written regarding the risk of the spread of infectious diseases related to global warming. In fact, there is some evidence that the Justinian plague was the product of global cooling. Five years before the onset of the pandemic, emissions from a volcano may have significantly lowered atmospheric temperature, resulting in the migration of rodents deprived of food. Fleas, which spread plague from rodents to humans, are unable to efficiently digest their blood meals at low temperatures, causing them to vomit as they attempt to feed again – injecting contaminated material into their hosts. 

The Justinian plague largely spared the Arabian Peninsula, thus nourishing the rise of Islam and Arab armies which easily went on to conquer large areas of a devastated Europe. 

From 1347 to 1351, a second plague pandemic – The Black Death – killed 75 to 200 million humans – an estimated ten-to-sixty percent of the European population. Once again, the disease originated in Asia, entering through Sicily on Genoese galleys, and reaching Venice in 1348. The irony of a pestilence from China spreading through northern Italy is obvious in light of current events. Just as the Justinian Plague claimed the life of Bishop Wighard, the Black Death killed two Archbishops of Canterbury in a single year – Thomas Bradwardine and John de Ufford.   

Just as the Justinian Plague altered the future of Europe, the Black Death may well have paved a path into the Renaissance.  

As of March 2020, there is little similarity between COVID-19 and Bubonic plague; but the current massive disruption of society will surely have consequences for human civilization in years to come.

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Read more on the global status of Major Coronaviruses

Read more on the global status of Plague

Death By Corona: What Are the Numbers?

   This morning, we learned that actor Tom Hanks and his wife have contracted COVID-19 infection. Indeed, 43 famous persons have already been affected by the disease, including six Iranian leaders and four European soccer players. We might speculate that this reflects a single exposure event in Iran…or the fact that European athletes travel frequently in a high-incidence environment. Perhaps similar reasoning can be used to explain the striking variation in coronavirus death rates between countries.

As of March 12, 126,258 cases of COVID-19 had been reported worldwide; and 4,368 died of the disease – a case-fatality ratio (CFR) of 3.6%. This figure varies widely from country-to-country. Indeed, The CFR in Mainland China is 3.9% – vs. 3.2% of all other countries combined. Only 1.0% of infected passengers aboard the Diamond Princess cruise ship died of the disease. Among countries reporting more than 500 cases to date, the CFR (in descending order) is Italy 6.6%, Iran 4.3%, Spain 2.8%, United States 2.8%, Japan 2.5%, France 2.1%, United Kingdom 1.7%, South Korea 0.8%, Netherlands 0.8% and Switzerland 0.7%. Fatal infection is notably rare among the Scandinavian countries: Sweden 0.2%, Norway 0%, Denmark 0%. Finland, which has experienced 109 cases, has reported zero mortality.

The CFR in each country is largely determined by how the disease is identified, defined and reported. The quality, training professionalism and available resources available Health-Care workers will also influence case-finding and treatment; as will Demographic and cultural differences related to age, nutrition, access to local health facilities, lifestyle and exposure to animals. I suspect that much of this variation in CFR for COVID-19 is related to the very definition of “cases”. The death of an infected patient will be obvious and easily documented; while asymptomatic or relatively minor infections could remain undocumented. Indeed, the total number of “cases” used to calculate CFR might only represent those cases who are sufficiently ill to seek medical care. The patient with a mild febrile illness will not be “counted”

These questions can be easily solved using a standard serological survey in relevant communities. Such a survey should include a questionnaire regarding recent symptoms, exposure, occupation, etc. If a large proportion of the general population is found to be seropositive toward SARS-2 virus, we might conclude that the disease is less dangerous than current statistics seem to indicate.

Histoplasmosis in Travelers

In 2019, several Canadian tourists acquired histoplasmosis while exploring caves in Cuba.  The Gideon database maintains an ongoing record of all cross-border Infectious Diseases events, including importation of animals and foods associated with zoonotic disease. [1-3]

As of 2019, 76 episodes of histoplasmosis had been associated with travel, involving at least 574 individual cases (8 fatal).  18 of these events were related to cave exposure, including two involving caves in Cuba.  Four publications described acquisition of histoplasmosis by Canadian travelers – two involving cave exposure.

In the following screen-shot, the frame to the left displays an interactive chronicle of cross-border histoplasmosis.  Users can sort data by year of event, country of exposure / origin, etc.  In this example I’ve selected “Setting” in order to study cases related to “cave exposure.”  Additional details and electronically-linked references appear when the user clicks on “Show event notes”

References:

  1. Gideon Online.  www.GideonOnline.com
  2. Berger S. Histoplasmosis: Global Status, 2019. Gideon e-books, https://www.gideononline.com/ebooks/disease/histoplasmosis-global-status/
  3. Berger S. GIDEON Guide to Cross Border Infections, 2019. 256 pages, 134 tables, 4,543 references.  https://www.gideononline.com/ebooks/travel/

Note featured on ProMED

Filgen distributes GIDEON in Japan

Filgen logoWe are pleased to announce that Filgen (フィルジェン株式会社) will be selling GIDEON in Japan.

Filgen, Inc. was founded in 2004 at Nagoya, Japan.
Filgen is a leading company of life science in Japan and offers various and cutting-edge analysis services by utilizing many technologies such as microarray, mass spectrometer, and next generation sequencing. The company also provides many biological reagents, instruments, and bioinformatics software. In addition, the company manufactures and provides machines for the nano-scientific field.

More information from Filgen about GIDEON

GIDEON at the Charleston Conference

On November 2nd, GIDEON will be exhibiting at the Charleston Library Conference.

Please stop by table 32 and meet Dr. Steve Berger to say hi or answer any questions you have.

 

 

GIDEON July webinar

EBSCO publishing will be hosting a GIDEON Webinar next week with Dr. Steve Berger, co-founder and Chief Medical Officer of GIDEON.
The session will consist of a 30-minute overview of all of the GIDEON modules, followed by a 30-minute live hands-on demo / question and answer session. Please join in and pass this on to colleagues.

Topic: Global Infectious Disease Informatics and Decision Support – A Case Study – July 2015

Date: Wednesday, July 29, 2015

Time
7:00 am, Pacific Daylight Time (Los Angeles, GMT-04:00)
10:00 am, Eastern Daylight Time (New York, GMT-04:00)
3:00 pm, GMT Summer Time (London, GMT+01:00)

Sign-in details
1. Go to https://ebsco.webex.com/ebsco/onstage/g.php?MTID=e81d311b6d7045a4ef510d32022f2d53f
2. Click “Join Now”.

GIDEON Sign In