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HERD IMMUNITY AND COVID-19

By Dr. Stephen A. Berger

Herd immunity concept. People of different age groups, men, women and children are protected from the harmful effects of viruses. Preventive measures, human protection, group immunity.

WHAT IS HERD IMMUNITY?

It stands to reason that a contagious disease should disappear from a population when a sufficient percentage of potential victims – “the herd” has become immune. This outcome may arise because a massive number of individuals have been either infected or vaccinated.

Most authorities dealing with COVID-19 have set the goal for herd immunity at >60 percent; however, the precise percentage for any infectious disease will depend on many factors involving demography, virulence, route of infection, etc. 

 

HAS AN INFECTIOUS DISEASE EVER BEEN ERADICATED BY REACHING HERD IMMUNITY?

Infectious Diseases have been known to reach herd immunity, however, none have been permanently eradicated by it. For instance, although there was an observed decrease of measles infections during the 1930s, recent outbreaks indicate the disease is far from being eliminated – despite effective vaccination measures introduced in 1963.

 

IMPORTANT CONSIDERATIONS

As many countries enter into a second-wave of this pandemic, the bottom-line question for those who advocate the achievement of herd immunity through mass infection of the population will be one of cost-benefit. 

This prompts a few thoughts and questions. Any program to actively infect large numbers of individuals will begin with the isolation of the elderly and other high-risk populations. How many countries are truly equipped to house, feed, isolate, and treat millions of people in these categories? Do they have the manpower, physical structure, and funding?

It is important to note that the 2002-2004 SARS outbreak was not brought to an end by herd immunity, but rather through stringent public health methods implemented by affected countries. 

 

HOW MUCH TIME WILL BE REQUIRED TO ACHIEVE HERD IMMUNITY?

My country (Israel) has a population of 8.8 million and is currently experiencing 1,000 to 2,000 new cases per day. If we allow the current disease rate to continue, it will take perhaps three more years (!) to exceed 60 percent immunity. 

Would the Health System – already at capacity – be able to sustain all of this? Is there proof that COVID-19 infection even leads to immunity?  In what percentage of patients? Does immunity persist for more than a year or two?  Will immunity also “cover” newer strains of coronavirus?

Several COVID-19 vaccines will be released for general use in the next three to six months. Assuming that these vaccines are effective, targeted mass-infection at this point will cause more harm than good… and at best be a case of “too little, too late.”

 

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Let’s end Polio

An Egyptian stele thought to represent a polio victim. 18th Dynasty (1403–1365 BC).
An Egyptian stele thought to represent a polio victim. 18th Dynasty (1403–1365 BC).

 

Poliomyelitis dates back to ancient times, as captured in this 14th century BC Egyptian carving, detailing a typical symptom of atrophy in one or more of the limbs. 

The modern name is directly derived from Ancient Greek, poliós meaning ‘grey’ and myelós meaning ‘marrow’, the latter signifying the effect on the grey matter of the spinal cord.

But while the ancient Egyptians and Greeks knew about the disease, it wasn’t clinically described until the late 18th century (AD), by the English doctor Michael Underwood. The disease was finally ‘formalized’ in the 19th century, thanks to the work of physicians Jakob Heine, who completed the first study on the disease, and Karl Oskar Medin, the first to detail the epidemic nature of Poliomyelitis. This led to the illness often being referred to as Heine-Medin disease.

SYMPTOMS

Polio is highly infectious and is spread through the fecal-oral exchange, mainly affecting children under the age of 5 but adult cases are not uncommon. Symptoms include fever, sore throat, headache, vomiting, and still neck.

Although the disease is feared for its more extreme outcomes, such as paralysis, these develop in only 1-2% of all cases. Less than 10% of cases are fatal, with as most infections being asymptomatic.

CAMPAIGN TO END POLIO

It is unknown how many deaths Polio has caused through the ages, but a significant global campaign has been in place since the 1950s as a response to the epidemic in the United States. 294,094 cases were reported from 1944 to 1953; 108,159 from 1954 to 1963; and 514 from 1964 to 1973. The campaign, combined with the effective vaccine, has led to the country being declared polio-free in 1979.

The establishment of the Global Polio Eradication Initiative (GPEI) in 1988 had a huge impact on the fight to end polio.  Over 2.5 billion children were vaccinated since then, with 20 million volunteers in 200 countries taking part in the campaign.

Fantastic progress has been made with wild cases dramatically reducing from an estimated global incidence of 350,000 in 1988 to only 33 reported cases in 2018 – but the work isn’t over yet. The infectious nature of the disease could easily lead to extensive outbreaks and see the numbers increase again, despite the effective vaccine, as has been recently observed with measles. 

Although Type 2 has not been detected since 1999, nine outbreaks of vaccine-strain virus infection were reported since the OPV2 withdrawal in 2016, posing a threat to its complete eradication. The last reported case of Type 3 was in Nigeria, back in November 2012.

 

Polio cases worldwide, 1996-today. GIDEON.
Wild polio cases worldwide, 1996 – today, GIDEON.

 

Now is the time for the final push to limit the disease to the history books (and databases). If you want to be a part of the solution, head over to End Polio Now and get involved! It could make the world of difference to those affected.

 

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Interested in learning more about this disease? Check out our 2020 eBook Poliomyelitis: Global Status 

Hepatitis A in the United States

Liver Infection with hepatitis viruses - 3d illustration

 

Few Americans are aware of a major epidemic that has taken hold of large areas of their country in recent years – by a disease that is easily diagnosed and prevented. Sadly, public – and even professional interest in these events have been overshadowed by COVID-19.   

AN UPTICK IN CASES

Hepatitis A had been largely under control until three years ago and can be easily prevented through the use of a safe and effective vaccine. 

From January 2017 to January 2019, at least 26 separate outbreaks were reported, to a total of 11,628 cases and 99 deaths, nationwide. Homeless individuals and users of illicit drugs accounted for a large percentage of these patients. 

The graph below shows that the number of reported cases, which had been declining steadily since 1997, has taken a dramatic upturn during the current epidemic. 

 

Hepatitis A cases in the United States, 1947 - today
Hepatitis A cases in the United States, 1947 – today

 

As of September 2020, more than 1,000 cases have now been reported in each of seven states: Florida, Georgia, Indiana, Kentucky, Ohio, Tennessee, and West Virginia. Indeed, the total number of cases reported since the arrival of COVID-19 in the United States has reached 6,650 (to October 10, 2020)  – a major concern to public health specialists.

 

WHAT ARE THE SYMPTOMS?

Hepatitis A is a highly contagious disease that affects the liver. Infection may cause symptoms such as vomiting, jaundice, anorexia, dark urine, and light stools, occasionally accompanied by rash or arthritis. Symptoms normally persist between two to eight weeks, although the illness may last longer and be more severe in patients with underlying conditions.

The case-fatality rate of Hepatitis A ranges from 0.15% to 2.7%, with children faring better than adults.

 

SUPPORTIVE THERAPY IS THE ONLY TREATMENT

At the time of writing, there is no known cure for Hepatitis A. To speed up recovery, it is recommended that patients get plenty of rest and avoid substances that may have adverse effects on the liver, such as alcoholic beverages and certain medications.

 

WHAT IS THE DIFFERENCE BETWEEN HEPATITIS A, B, AND C?

Even though there is no drug therapy against Hepatitis A, it is less dangerous than Hepatitis B and C.

While most Hepatitis A patients recover with lifelong immunity to the disease, Hepatitis B and C may ‘reappear’ in the form of hepatic cirrhosis or hepatocellular carcinoma years after the acute illness. 

Hepatitis B is responsible for 60% to 80% of the world’s primary liver cancer cases. Thankfully, its rates continue to decline in  the United States:

Hepatitis B cases in the United States, 1966 - today graph
Hepatitis B cases in the United States, 1966 – today

 

The mode of transmission also differs among the three viruses. HepA is transmitted via the fecal-oral route, HepB, and HepC through the exchange of infected bodily fluids. 

As of 1998, injecting-drug abuse accounts for 60% of Hepatitis C transmission in the United States:

Hepatitis C cases in the United States, 1992 - today graph
Hepatitis C cases in the United States, 1992 – today

 

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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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Disease names – what do they mean?

Medical dictionary with disease names

In the midst of the continuing pandemic, World Dictionary Day seems like the perfect occasion to consider the meaning and origin behind some of the most well-known disease names. We’ve been speaking with Dr. Steve Berger, our co-founder, to learn more.

CORONAVIRUSES

Let’s start with the obvious one. COVID 19, which began as a localized outbreak of “Novel Coronavirus” infection,  is now a name almost every household in the world will know. COVID-19 comes from COrona VIrus Disease which first appeared in 2019, with the disease itself being caused by the SARS-CoV-2 virus.

SARS was a prominent name back in the early 2000s, with a simpler acronym Severe Acute Respiratory Syndrome. 

The names of COVID-19 and SARS-CoV-2 have been used throughout mainstream media, but not without a certain degree of confusion, which is similar to the one sometimes seen with HIV and AIDS. A useful analogy is that the Human Immunodeficiency Virus (HIV) causes Acquired Immunodeficiency Syndrome (AIDS) much like SARS-CoV-2 causes COVID-19.

A lesser-known fact outside of the medical community is that there are many different species of a type of virus. Each type is given a name derived from the kind of virus it is and often its discovery whereabouts. As of 2020, seven coronavirus species have been associated with human disease:   

  •       HCoV 229E 
  •       HCoV OC43 
  •       SARS-CoV 
  •       HCoV NL63 (New Haven coronavirus) 
  •       HCoV HKU1 
  •       MERS-CoV (the Middle East Respiratory Syndrome coronavirus) 
  •       SARS-CoV-2 

 

TYPES OF DISEASE NAMES

Not all diseases are given acronyms and the discordance between the name of the virus and the name of the disease is unusual. In many cases, viruses that infect humans are named for the disease that they cause. For example, poliomyelitis is caused by the poliomyelitis virus, while influenza is caused by the influenza virus. 

Disease names themselves are typically taken from either the area of the body it affects, or where it was discovered, or who discovered it. 

For instance, poliovirus’s name is derived from the Ancient Greek poliós, meaning grey, as it attacks nerve cells located in the grey matter at the center of the spinal cord. Influenza originates from the Italian term for influence. It was believed the illness was caused by ill omens from the sky, just as it was thought that another infectious disease, malaria, was caused by foul swamp air (mala aria).

Even the current pandemic has symbolic origins for its name, as the virus resembles a crown (Latin, corona) under the electron microscope. Similarly, rotavirus, a common cause of childhood diarrhea, resembles small wheels (Latin, rota). 

The Ebola disease, on the other hand, takes its name from the village it was first discovered, near the Ebola River in the Democratic Republic of Congo in 1976. Likewise, the West Nile virus was first identified in the West Nile District of Uganda in 1937; and the Zika virus in the Zika Forest of Uganda during the 1940s. Two of the coronaviruses identified this year are named after the places they were first reported in: New Haven, Connecticut, and the Middle East. 

 

A DOUBLE-EDGED SWORD

The naming of a pathogen for the region it was discovered can be stigmatizing and have geopolitical ramifications. The World Health Organization made a point to exclude the terms “Wuhan” and “China” when naming the current pandemic disease. Even the naming of disease after the discovering professional, or in someone else’s honor can be considered contentious, as is the case with Listeria. 

Listeria, found in contaminated food, was named after Joseph Lister, who pioneered hospital health standards throughout his career. He championed the use of early antiseptics, and even such novel ideas as washing hands… Imagine needing to justify the benefits of cleanliness in a hospital! However, during his career, Lister was shunned for his approach despite proving it hugely successful in preventing surgical mortality. 

Would you consider it an honor to have your name immortalized in the naming of a species, even if it is a bacteria? 

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“Under the radar” – Ongoing Lassa Fever Outbreak

By Dr. Stephen A. Berger

Stethoscope on Africa map
Nigeria is battling the largest recorded Lassa Fever outbreak to-date

 

Lassa Fever in Nigeria is a paradigm for Infectious Disease outbreaks that continue to threaten massive populations “under the radar” during the COVID-19 pandemic. As of October 3, 2020, a total of 1,112 fatal cases of COVID-19 had been reported in Nigeria.

In terms of population size, the statistical likelihood of dying from this disease in Nigeria – or in Singapore – is exactly the same. But then…nobody in Singapore is dying these days from Lassa Fever.    

WHAT IS LASSA FEVER?

The disease was first recognized in 1969, in northeastern Nigeria. The virus is acquired from African rodents and their secretions, primarily the Multimammate rat (Mastomys natalensis) which is its natural reservoir. A secondary person-to-person transmission can occur through contact with infected bodily fluids.

The illness is characterized by fever, pharyngitis, headache, chest pain, and diarrhea. 

Leukopenia, proteinuria, and hepatic dysfunction may also be present. Permanent hearing loss is common – indeed, this disease is the most common cause of acquired deafness in West Africa. Reported case-fatality rates range between 15-25%.

Multimammate rat (Mastomys natalensis)
Multimammate rat (Mastomys natalensis), a reservoir of Lassa Fever

DISTRIBUTION

It is estimated that as many as 500,000 individuals are infected in West Africa each year, resulting in 5,000 deaths. During the past 50 years, at least 88 travelers have returned home to other countries with this disease – including 11 importations into the United States. 

An ongoing outbreak of Lassa Fever continues in Nigeria well into 2020 – with 5,527 cases (222 fatal) reported as of August 16…all against the background of COVID-19.

Lassa Fever outbreaks map 2018-2020
Recent outbreaks map, 2018-2020, GIDEON

 

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Monkeypox

By Dr. Stephen A. Berger

 

Cynomolgus monkey, a known reservoir of the Monkeypox virus
Cynomolgus monkey, a known reservoir of the Monkeypox virus

 

WHAT IS MONKEYPOX?

Monkeypox, as the name implies, is a disease of monkeys (unlike chickenpox – which has no relation to chickens). Although the condition is reported in a group of eleven African countries, the virus was first discovered in a laboratory in Denmark in 1958, when it was first isolated from cynomolgus monkeys.

The signs and symptoms are similar to those of smallpox. Following a three-day prodrome of fever, headache, myalgia, and back pain, patients develop a papular rash in the face, extremities, and genitals. The rash then spreads outward to involve the face, with lesions evolving into umbilicated pustules. 

Unlike smallpox, death from monkeypox is relatively uncommon – five-to-ten percent.

Palms of a monkeypox patient
This 1997 image was created during an investigation into an outbreak in the Democratic Republic of the Congo (DRC) and depicts the palms of a monkeypox case-patient. It is important to note how similar this maculopapular rash appears to be when compared to the rash of smallpox, also an Orthopoxvirus. Image courtesy of CDC/Dr. Brian W.J.Mahy

NOTABLE OUTBREAKS

During the single year of 1967, almost eleven thousand cases occurred in West and Central Africa. 

The most unusual outbreak of monkeypox occurred in 2003 when 81 humans in the American Midwest were infected through contact with infected prairie dogs – themselves infected by rodents that had been imported from Ghana. Fortunately, all patients recovered without sequelae. By coincidence, the iconic outbreak of SARS was also reported at this time – perhaps, as in the current COVID-19 pandemic, distracting media attention from events surrounding other diseases. 

During 2018 to 2019, five Nigerian travelers were found to have monkeypox – in Israel, Singapore, and London. 

 

A RECENT RISE IN CASES

The viruses of monkeypox and smallpox are biologically similar. Indeed an attack of one will immunize the patient against the other. Thus, rates of monkeypox were low during the period that smallpox vaccination was widely used in Africa, while the discontinuation of vaccination has been followed by a resurgence of monkeypox cases. 

These developments are well illustrated by an ongoing outbreak of monkeypox that has persisted well into the COVID-19 pandemic. From January 1 to September 13, a total of 4,494 cases of monkeypox (171 fatal) were reported in the Democratic Republic of Congo.

 

Monkeypox cases in the Democratic Republic of Congo
Cases in the Democratic Republic of Congo, 1970 – 2019

 

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Antigen vs antibody – what is the difference?

Antigen vs antibody - 3D illustration
3D illustration of antigen in the human body

 

What is the difference between antigen vs antibody, and what role do they play in creating an effective vaccine? With the recent focus on the development of a COVID-19 vaccine there has been much talk of antigens and antibodies, often interchangeably, and little clarity on what they are – or the role they play in creating an effective vaccine. In this blog, we’ll cut through the jargon and discover the facts together.

Antigen

An antigen is any substance or organism that is unrecognized by our immune system. It could be anything from bacteria to chemicals, to viruses … or even foods [1]. Antigens typically trigger an immune response, which may consist of an antibody (more on that later), and are classified by their origins [2]:

  • Exogenous: entering from outside the body
  • Endogenous: generated from within
  • Autoantigens: proteins targeted in autoimmune diseases
  • Neoantigens (or tumor antigens): resulting from tumor cells.
  • Native antigens: An antigen which will later be processed by an antigen-presenting cell

In some cases, these main types have subtypes – but we won’t get into an immunology lecture today. An antigen-presenting cell is a cell that processes and then presents the antigen to T-cells (a form of white blood cells), which can then ‘handle’ the antigen, often by killing the offending cell [3].

Your immune system has “memory” which allows the system to deal with the offending antigen much more quickly and efficiently the next time it is encountered.  Vaccines are designed to simulate that first encounter with an antigen and create a robust memory in case the offending agent reappears in the future. [4].

The importance of vaccines is covered in more detail here, but in short, antigens themselves are crucial in the development of vaccines. Generally, the vaccine consists of a potentially hostile antigen, in a very weak or inactive form.

Antibody

Antibodies are proteins that bind with the antigen in order to neutralize the latter – or make other elements of the immune system “aware” of their presence.  Antibody-producing cells are specifically designed to tackle one type of antigen; and your blood, bone marrow, lymph glands, and spleen will contain millions of them to ensure that every known antigen will be confronted by a corresponding antibody  [5].

Antibodies are secreted by B leukocytes (a form of white blood cell) and circulate in blood plasma either freely or attached to the surface of a B cell.  The B and T cells work in unison to identify and locate antigens, create the correct antibodies, and capture (kill/neutralize) the antigen [6].

A vaccine, by exposing the immune system to a new antigen, will “teach” antibodies the correct format in which to capture or tag that antigen.  When the actual disease antigen later enters the body, the immune system will rapidly respond with minimal discomfort and inconvenience.

Effective vaccination needs both

To summarize – an antigen is a disease agent (virus, toxin, bacterium parasite, fungus, chemical, etc) that the body needs to remove, and an antibody is a protein that binds to the antigen to allow our immune system to identify and deal with it.

Woman with adhesive bandage on her shoulder
Antigens and antibodies work in tandem when vaccinating

 

Don’t take this all for granted, though. As impressive as our immune system is, it’s far from perfect and needs our assistance to prevent harmful antigens from entering the body – through hand washing, face masks, and social distancing. Look after your body and it will look after you!

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References:

[1] M. Encyclopedia, “Antigen: MedlinePlus Medical Encyclopedia”, Medlineplus.gov, 2020. [Online]. Available: https://medlineplus.gov/ency/article/002224.htm

[2] “Antigens | Boundless Anatomy and Physiology”, Courses.lumenlearning.com. [Online]. Available: https://courses.lumenlearning.com/boundless-ap/chapter/antigens/. 

[3] T. Kambayashi and T. Laufer, “Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell?”, Nature Reviews Immunology, vol. 14, no. 11, pp. 719-730, 2014. Available: 10.1038/nri3754 

[4] A. Abbas, A. Lichtman and S. Pillai, Cellular and molecular immunology, 9th ed. Philadelphia: Elsevier, 2018, p. 97.

[5] C. Janeway, Immunobiology 5: the immune system in health and disease, 5th ed. Garland Publishing.

[6] L. Borghesi and C. Milcarek, “From B Cell to Plasma Cell: Regulation of V(D)J Recombination and Antibody Secretion”, Immunologic Research, vol. 36, no. 1-3, pp. 27-32, 2006. Available: 10.1385/ir:36:1:27

Rabies – a dumb disease

Vaccine Rabies Bottle and Syringe Needle Hypodermic Injection,Immunization rabies and Dog Animal Diseases,Medical Concept with Dog blurred Background.Selective Focus Vaccine vial
Dog vaccination programs are the most effective way to prevent Rabies

 

Rabies is endemic to over 150 countries, and according to the World Health Organization, 99% of all transmissions to humans are from dogs, potentially bringing into question the animal’s status as the ‘man’s best friend’. 

In Europe, southern Africa, and parts of North America, most cases are acquired from wild carnivores; mongooses, and vampire bats in Latin America and the Caribbean. In more recent years, humans have acquired rabies from inhalation of aerosols in bat caves, ingestion of dogs and cats for food, ticks, cart-scratches, and inadvertent transplantation of corneas or internal organs from infected donors. 

In recognition of World Rabies Day, we have asked our co-founder, Dr. Stephen Berger, for his take on the disease. He didn’t hold back with the assessment!

“Rabies, from an evolutionary standpoint, is a truly “stupid” disease. Most animals with Rabies virus infection become paralyzed and die – thereby preventing the survival and reproduction of the virus itself. Ebola and Smallpox, albeit highly contagious, are also “stupid” in this respect,” said Dr. Berger, highlighting an interesting point.

When a disease limits its access to new hosts, how does it survive and continue to spread?

How long before it’s too late?

Virus transmission takes place via exposure to infected saliva, not necessarily a bite –  although bites are the most common means of transmission. The virus is very active in moist conditions but quickly becomes non-infectious when dried or exposed to direct sunlight.

In dogs, the virus incubates for between 2 weeks to 4 months before the animal can transmit the disease.

In human cases, the incubation period can be as short as a few days or take as long as a few months for the disease to become active and symptoms to show.  In rare cases, Rabies has appeared as long as five years following an animal bite.  Once symptoms appear, the case-fatality rate is virtually 100%. As of 2014, only 13 cases of human survival from rabies had been documented.

Two forms of Rabies

The disease has two recognized forms – Furious and Paralytic, also known as ‘dumb Rabies’. In the furious form, dogs (or humans) froth at the mouth and display extreme hyperactivity. Patients often develop spasms when exposed to water – thus the term “hydrophobia.”  In some cases, a similar response will follow fanning the patient – “aerophobia.”

While Furious Rabies is most familiar to the lay public (thanks to the cinema and TV)  the Paralytic form often predominates among dogs. This type causes a slow progression from difficulty swallowing to full-body paralysis and eventually, death.

Rabies is 100% vaccine-preventable

When compared to diseases such as Tuberculosis, where symptoms such as coughing actively support transmission through the projection of infectious material into the air, Rabies would seem easier to control, especially when effective preventative and therapeutic vaccines and immune-globulins are available. 

The disease was recorded as far back as 556 BC, in China, and a viable vaccine has existed since 1885. The World Health Organization (WHO) considers the disease to be one of the Neglected Tropical Diseases, in part due to the under-usage of effective vaccination, which works even after the virus has entered the body.  A lesser-known adjunct to therapy is vitally important, but not as well-known to the public. Thorough cleansing of a wound using soap and water has been shown to reduce the incidence of Rabies by 50% following the bite of a rabid animal!

Sadly, despite the fact that 29 million people receive the vaccine every year, thousands still die from the disease. 95% of deaths occur in Asia and Africa, with children under the age of 15 making up 40% of all cases. 

Stray dogs present a significant problem in countries such as India, Namibia, Angola, Mozambique, and Kenya, where annual disease rates exceed 0.2 per 100,000 population.

WHO leads a collective “United Against Rabies” campaign to drive progress towards zero human deaths from dog-mediated Rabies by 2030.

Rabies distribution and outbreaks map, 1709 - 2020
Rabies distribution and outbreaks map, 1709 – 2020

 

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Penicillin: the accident that saved many lives

Fleming in his Lab - Photo. Date: 1881 - 1955
Alexander Fleming in his laboratory, 1881 – 1955

 

There have been many happy accidents in science. Several of these were of great benefit to medicine.

For example, in 1895, a German physicist working with a cathode ray tube happened to place his hand in front of the rays and found that he could see his bones in the image projected onto the screen. Soon after that, the first X-ray images were produced.

There have been other instances where serendipity played a role in unearthing effective treatments against diseases. 

 

THE FIND OF THE 20TH CENTURY

The most famous of these happy accidents is the discovery of Penicillin as an antibiotic remedy. 

Alexander Fleming, a Scottish bacteriologist, worked at the inoculations department at St Mary’s Hospital in the early 1900s. 

In September 1928, Fleming had left a pile of bacteria cultures in his laboratory before going on holiday with his family. The cultures he was studying were known to cause septic infections. By accident, he left one of the Petri dishes uncovered.

Fleming returned to find that a bluish-green mold, similar to the mold found on bread, had contaminated the specimen. The area around the mold in the Petri dish was clear of bacteria. 

Fleming observed that the mold seemed to have killed the germs. This mold was identified as a strain of Penicillium. He saw this as a potential treatment for bacterial infections. 

Penicillin culture,1929
Penicillin culture, 1929

 

IMPORTANCE OF SHARED SCIENCE

Fleming was able to further identify that it wasn’t just the mold that killed the bacteria but the ‘juice’ the mold seemed to produce. 

He also discovered that the ‘mold juice‘ was effective against pathogens that are responsible for diseases like Meningitis, Diphtheria and Gonorrhea. 

Fleming’s effort would bear no further fruits. He was not able to produce and purify the ‘mold juice’ in substantial quantities.

However, he named the substance Penicillin and published his findings in the British Journal of Experimental Pathology in 1929. This crucial step allowed others to build on his work.

A decade later, Fleming’s findings piqued the interest of two Oxford scientists: Howard Florey and Ernst Chain. Eventually, they found a way to mass-produce the antibiotic in a form that could kill harmful bacteria without having any toxic effects on the human body.

Vintage vials of Penicillin G
Vintage vials of Penicillin G

 

PENICILLIN’S WARTIME VALUE

During World War I, Alexander Fleming was stationed in France and served in the Army Medical Corps as a captain. He observed that the death of soldiers was not always from wounds inflicted in battle, but rather from bacterial infections.

The principal treatment of such infections consisted of the administration of antiseptics. Fleming noted that these often did more harm than good. He wrote about this, however, his findings were not taken seriously at the time.

During World War I, the death rate from bacterial pneumonia was 18%. In WWII, thanks to Penicillin, the death rate from the same condition fell to less than 1%. This enabled many soldiers to return home in good health.

 

AN EXCEPTIONAL DISCOVERY

The mass production of Penicillin is credited with saving the lives of many thousands of soldiers during World War II. 

Antibiotics of the Penicillin family have been found to cure a wide variety of bacterial infections from mild, moderate upper respiratory tract infections to skin ulcers and urinary tract infections.

In 1944, Alexander Fleming was knighted by King George VI. In 1945, he received a Nobel Prize in Physiology or Medicine, together with Howard Florey and Ernst Boris Chain. 

The praise was well deserved, as infections that were once life-threatening are now only mild inconveniences because of Penicillin’s versatility and efficacy. Penicillin richly deserves its place as one of the most important anti-infective drugs of all time.

Interestingly, Fleming was not the first to observe the antibacterial effect of Penicillium. Between 1868 and 1873, a famous surgeon named Theodor Billroth discovered that it inhibited bacterial growth – but nothing was done about it at the time. He died when Fleming was 13 years old.

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Learn more: GIDEON Guide to Antimicrobial Agents

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