The Zombie Apocalypse

Is this the beginning of the end? Will humanity, as we know it, unravel and collapse as we are ripped apart by man-eating corpses? Probably not. At the very least, our cultural obsession with the world ending in a gruesome manner would finally be put to an end – no need for renewals of The Walking Dead. As interesting as an imminent zombie apocalypse may sound, fear not: – we are still safe – for now.  

‘Zombie deer disease’ is the clickbait term for chronic wasting disease (CWD) – a transmissible, neurodegenerative disorder. Currently, the CWD outbreak appears to be limited to cervids, which are deer, elk, moose and the like. The symptoms are progressive weight-loss, decreased social interactions, lack of coordination, loss of fear for humans and more aggressive behaviour.  It’s easy to see why the term ‘zombie deer disease’ caught on, although the truly frightening fact is that CWD is an infectious prion disease which is incurable and ultimately fatal. We will delve into what a prion disease is in a moment – does ‘mad cow disease’ sound familiar?

This isn’t the first time that CWD cases have been reported. In fact, it was first identified in the late 1960s in mule deer and black-tailed deer held in captivity in Colorado and later in Wyoming. The reason behind the sudden furore now, is that currently the number of CWD cases detected is on the rise and is spreading to areas previously devoid of the disease, as well as being identified now in both captive and free-ranging cervids.

As of March 6, 2019, CWD in free-ranging deer, elk and/or moose has been reported in at least 24 states in the continental United States, as well as two provinces in Canada. In addition, CWD has been reported in reindeer and moose in Norway and Finland, and a small number of imported cases have been reported in South Korea.”

– Centers for Disease Control and Prevention

There is a rapidly growing concern regarding the transmission from the infected cervids to other wild animals and possibly to humans. As mentioned before, CWD is a prion disease to which there is no vaccine or treatment present if the disease were to jump from cervids to humans.

So, what is a prion disease?

Prions are infectious agents which are responsible for a group of always fatal neurodegenerative disorders. The term ‘prion’ is an acronym derived from proteinaceous and infectious particle. These protein-only particles were initially hypothesised, by Stanley B. Prusiner, to be the infectious agents of scrapie – a neurodegenerative disorder, which causes sheep to pathologically scrape against fences, among other altered behavioural traits. Prusiner accumulated data supporting his ‘protein only’ hypothesis which was only accepted years later by the scientific community – a common trend – and he was awarded a Nobel prize for his work on prions.

The Nobel Prize in Physiology or Medicine 1997 was awarded to Stanley B. Prusiner “for his discovery of Prions – a new biological principle of infection.”

– Nobel prize organization

So now that we have clarified that prions are simply infectious proteins, it is equally important to understand that the normal non-infectious version of the prion protein is also referred to as a prion. It is unfortunate, that the normal cellular prion protein has been given the same name as the infectious agent associated with a group of fatal neurodegenerative disorders.

Normal prion proteins are produced by mammalian cells, secreted and localised at the cell surface. The highest levels of the protein are located in neurons of the brain and spinal cord – indicating a possibly important physiological role. Even though much research has gone into prion diseases, the actual function of normal prions remains unknown. It has been suggested, through various studies, to be involved in the protection of cells against internal and environmental stresses.

When normal prion proteins misfold, the properties of the protein changes and the misfolded form is associated with disease. Not only does the misfolded protein begin to accumulate and clump together, it also interacts with other normal prion proteins and causes them to misfold. Since the highest levels of normal cellular prion proteins are in neurons, the spread of the infectious prion between neuronal cells leads to brain damage.

Extracted from http://biology.unm.edu/toolson/biotox/presentations/mechanism.html

Figure 1: Showing how a prion disease develops, the normal prion protein (PrPc) interacts with a diseased form (PrPsc), which is present due to either spontaneous misfolding of the normal protein, a genetic mutation or inoculation with the diseased form such as from eating contaminated meat.

How is it transmitted?

To investigate how transmission occurs between cervids, Mathiason et al. exposed 4 cohorts of 6-month-old CWD-naive hand-raised white-tailed deer (Odocoileus virginianus) fawns to saliva, blood, a combination of urine and faeces and brain homogenate from CWD-positive deer. The infectious CWD proteins were detected in deer inoculated with saliva, blood and brain homogenate.  Their results suggest that deer in high density populations and in captivity would most likely facilitate salivary transmission of prion disease. This result does however need to be viewed with caution as a small sample size was used and therefore factors such as individual susceptibility may account for these results.

Is it transmissible to humans?

The answer is, unfortunately, not a simple yes or no as the debate is still on-going. On the one hand, there are some who strongly advocate that transmission will occur.

It is probable that human cases of chronic wasting disease associated with consumption with contaminated meat will be documented in the years ahead.”

Michael Osterholm, director of the Center for Infectious Disease Research and Policy

Support of this claim comes from a previous case similar to that of CWD. There was an outbreak of Bovine Spongiform Encephalopathies (mad cow disease) in the United Kingdom, over two decades ago, resulting in 4.4 million cattle being slaughtered. As with CWD now, mad cow disease was also believed to not be able to spread to humans. John Gummer (Minister of Agriculture at the time) had announced that beef was “completely safe”.  It turned out that the prion disease was in fact transmissible to humans resulting in Variant Creutzfeldt-Jakob disease (or vCJD), a fatal condition.

Since 1995, when it was identified, 178 deaths have been attributed to vCJD. It’s thought that one in 2,000 people in the UK is a carrier of the disease. But it appears that relatively few who catch the infectious agent that causes the disease then go on to develop symptoms.”

BBC news

Even though mad cow disease is transmissible to humans, that does not necessarily dictate that CWD will be as well.  The transmission of prion diseases from animals to humans varies with different species and prion proteins. Several studies have investigated the possibility of transmission of CWD to non-human primates, such as in cynomolgus macaques. The cynomolgus macaque monkeys are used as a surrogate model for CWD transmission to humans.

A study published in the Journal of Virology looked at transmission from cervids to monkeys from two different genera. They found that oral inoculation of brain homogenate resulted in 92% of squirrel monkeys (Saimiri sciureus) to develop disease, at an average of 69 months post-inoculation, but none of the cynomolgus macaques (Macaca fascicularis) developed disease. This interesting result suggests that there is a species barrier between cynomolgus macaques and cervids but not between squirrel monkeys and cervids. Compared to squirrel monkeys, the prion protein of cynomolgus macaques is more similar to humans. It was suggested that the differences in the prion protein sequence between the squirrel monkey and cynomolgus macaques is linked to disease susceptibility. Of the 5 amino acids that differ between the two monkey genera, 3 of those that are found in cynomolgus macaques are identical in humans. Even after 13 years post-inoculation, there was no evidence that CWD transmission had occurred to the macaques using clinical detection and using highly sensitive prion disease-screening assays. This study agrees with various other studies suggesting humans are at a low risk of contracting CWD.

The media has the distasteful tendency to sensationalise the disease, causing panic to get traffic, while simultaneously providing little information which is often misguided, misquoted or simply exaggerated. Unlike the data regarding the mad cow disease which showed compelling evidence that prions from cattle with BSE have infected humans and caused fatal neurodegeneration, the data regarding CWD involves multiple studies, including seven tube-based experiments, five studies on transgenic mice, two epidemiologic studies and nine case studies all showing no conclusive link between CWD exposure and the development of a prion disease in humans. With that being said, beware of misquoted science and fake news and revel in the zombie apocalypse-free world.

To date, there have been no reported cases of CWD infection in people.”

The Centers for Disease Control and Prevention

References

Photo of Winter Herd – Elk, in National Elk Refuge, Jackson Hole, Wyoming, courtesy Thomas D. Mangelsen (mangelsen.com)

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What about Ebola?

Part 1: Has the world abandoned Ebola?

Ebola is a recurring tragedy. Once again it is in the news, though this time not many have noticed.  As you may have guessed from the tone used, it’s not due to its eradication. The world’s second largest Ebola outbreak is occurring – of which the global press has taken scant notice. Yet, Ebola’s seriousness and recurrence begs the question – why have we not overcome this disease? Ebola has over the last 40 years been a source of excruciating pain and loss to many people. However, political and socioeconomic problems in the affected areas have made eradication a monstrous challenge. Also worrisome is the growing apathy of the western world towards the situation, which may be why the recent Ebola outbreak barely reached the news ­– it is seemingly no longer a front burner issue for the media.

Still, this time, on the 17th July 2019, the World Health Organisation declared that the Ebola outbreak in the Democratic Republic of Congo (DRC) is ‘a Public Health Emergency of International concern’.  This announcement was made shortly after the report of the virus being detected in Goma, a densely populated city of 2 million people in the eastern DRC, situated on the Rwandan border. The current threat, now present at a major transportation hub near an international border, once again underlines the urgency of increased medical staff on the ground, screenings, and further international funding. However, this year-long Ebola outbreak hasn’t received the attention of previous outbreaks, over a decade ago. A combination of difficulties reporting on this outbreak from conflict areas of the DRC, donor fatigue and killings of on-site medical staff may be just some of the reasons why.

The negative effect of intrinsic distrust

It is difficult to trust anyone, when you are living in a country with a history of conflict, corruption and trauma. The DRC, since gaining independence, has been engulfed in two wars claiming millions of lives from fighting, disease and malnutrition. Years later and there is still on-going conflict in certain areas due to various rebel groups, resulting in further displacement of families and the recruitment of children by armed groups to be child soldiers.

Aggravating these problems are the clashes between medical strategies and local customs such as burial rituals, clashes which are fuelled by conspiracy theories such as Ebola being released by the current president; or by foreigners. These deep-seated myths are extended to health workers that are accused of injecting deadly substances.

when you go there they inject you with the disease

Vahavi (30)

A study published in The Lancet surveyed the level of distrust of the locals in an active zone of the Ebola outbreak. Of the 961 participants surveyed, almost half (45.9%) of the respondents believed in the misinformation that either Ebola does not exist, is fabricated for financial gains or is fabricated to destabilize the region. These thriving rumours have led to the murder of 25 reporters and imprisonment of 239 in 2019 alone, as well as threats, attacks and killings of health workers either in their line of work or in their homes.

The locals’ distrust towards both the government and outsiders is one of the key reasons for the slow progress in tackling Ebola. The weakened political situation and dwindling pool of aid from western countries are making eradication efforts tremendously difficult. The violence and political instability have caused many nongovernmental organisations to pull out from the country completely. Furthermore, there is an overall rise in populism within donor countries causing them to turn their attention inward. The battle against Ebola now seems far from over.

Is there a cure or treatment?

As of 27th August, the year-old DRC outbreak has resulted in a total of 2 997 cases being reported, of which 1 998 died – bringing the grand total to 30 000 cases of Ebola and 11 000 deaths since 1976. The pursuit for an effective treatment accelerated following the 2014/2016 outbreak in West Africa. Nearly 170 000 people have been vaccinated with rVSV-ZEBOV, a currently commercially unlicensed vaccine which has been approved by the DRC government for ‘compassionate use’. Other medicines falling under this category include 3 different antibody treatments, mAb114, ZMapp and REGN-EB3. An antiviral drug, remdesivir is also being tested in the latest outbreak.

A Congolese health worker administers Ebola vaccine to a child at the Himbi Health Centre in Goma, Democratic Republic of Congo, July 17, 2019.
Olivia Acland | Reuters

A randomised, controlled clinical trial, Pamoja Tulinde Maisha (PALM [together save lives]) has been investigating four agents: ZMapp, remdesivir, mAb114 and REGN-EB3 since 20 November 2018. However, because preliminary results indicated that patients receiving REGN-EB3 or mAb114 had a greater chance of survival than the participants using the other two candidates, the independent data and safety monitoring board (DSMB) recommended that the study be halted. While the final analysis of the data will only occur in September/October 2019, when all the data has been generated and collected, the preliminary analysis of the existing data was thought to be compelling enough to implement changes immediately. Whether this was the right call is yet to be seen. However, announcement of these results has already sparked celebratory comments.

“From now on, we will no longer say that Ebola is incurable,” said Dr Muyembe, the doctor whose original research has resulted in the making of the two promising treatments. “I’m a little sentimental. I had this idea a long time ago, and I’ve waited patiently for it. I’m very happy, and I can’t believe it.”

Although the latest advancement in the battle against Ebola may seem grand, Ebola will unlikely be eradicated in the upcoming months, due to the deep-rooted problems within the country and its relationship with the West. Political scientist, Phil Clark, described the timing and location of the outbreak as an “unfortunate coincidence.” However, the progress reported in treating Ebola is by no means trivial. Tribute must be given to those involved in fighting against the current outbreak who “put their lives on the line every day to care for patients in extremely difficult conditions in the area where the outbreak is occurring,” which has resulted in many lives being saved.  

To understand about how Ebola effectively attacks the immune system and brings about uncontrollable bleeding, read part 2 of ‘What about Ebola?’.

Featured image: A health care worker carries a baby suspected of being infected with Ebola virus in a hospital in Oicha, North Kivu Province of Democratic Republic of Congo, December 6, 2018. REUTERS|Goran Tomasevic

References

https://blackagendareport.com/new-ebola-drugs-show-exciting-promise-90-percent-cure-rate

https://rsf.org/en/barometer

https://www.businessinsider.com/ebola-virus-timeline-possible-cure-2019-8?IR=T

https://www.nbcnews.com/news/world/congo-s-ebola-response-threatened-conspiracy-theories-rumors-n994156

https://www.nih.gov/news-events/news-releases/independent-monitoring-board-recommends-early-termination-ebola-therapeutics-trial-drc-because-favorable-results-two-four-candidates

https://www.pri.org/stories/2019-07-03/dr-congo-ebola-rumors-may-spread-faster-virus

https://www.scientificamerican.com/article/where-does-ebola-come-from/

https://www.thelancet.com/action/showPdf?pii=S1473-3099%2819%2930063-5

https://www.who.int/news-room/detail/29-08-2019-as-ebola-cases-reach-3000-in-drc-who-calls-on-partners-to-fulfill-promises-to-communities

The Measles Crisis

A contagious disease that was once thought to be contained, has been let loose. That the comeback of measles is here is certain. The only question now is – to what extent. The World Health Organization has released their preliminary global data, reporting that cases have risen by 300% in the first 3 months of 2019 – a staggering increase in this highly infectious and potentially deadly disease. The cause can be attributed to two things: lack of vaccines in developing countries and the result of misinformation spread by anti-vaxxers.

In countries beset with poverty, the lack of resources has led to the latest epidemics, with only a portion of the population vaccinated and further attempts complicated by conflict, overcrowding, poor access to medical care and malnutrition. By way of example, Madagascar is currently facing its worst measles epidemic in history. As of 14 April 2019, more than 115 000 cases have been reported and up to 1 200 individuals have died. In first world countries, where parents have the opportunity to protect their children, the spike in cases has been fuelled by misplaced beliefs in false information i.e. the anti-vax movement, which causes parents to balk at vital vaccines, leaving their children vulnerable.

Current outbreaks include the Democratic Republic of the Congo, Ethiopia, Georgia, Kazakhstan, Kyrgyzstan, Madagascar, Myanmar, Philippines, Sudan, Thailand and Ukraine, causing many deaths – mostly among young children.

World Health Organization

The number of cases is spreading quickly in countries with high immunisation rates such as the United States, Thailand, Israel and Tunisia. In the United States, there have been 704 cases reported in 22 states, as of 26 April 2019. When a significant proportion of the population is vaccinated then transmission of the disease is unlikely, as there are fewer individuals to infect, effectively stopping the spread of the disease in the community, allowing unvaccinated individuals to be protected by so called ‘herd immunity’. In the case of measles, herd immunity occurs when 95% or more of the population is vaccinated. Decline in measles vaccine coverage has resulted in the current outbreaks which are responsible for the deaths of many, mainly children.

Complacency about the disease and the spread of falsehoods about the vaccine in Europe, a collapsing health system in Venezuela and pockets of fragility and low immunization coverage in Africa are combining to bring about a global resurgence of measles after years of progress.

Dr Seth Berkley, CEO of Gavi, the Vaccine Alliance

Should we be concerned?

Measles is a contagious viral disease caused by infection with the rubeola virus. An infected individual can spread the disease 4 days before developing a rash and 4-5 days after the rash appears through physical contact, coughing, sneezing or touching infected surfaces. The virus is able to remain active and contagious in the air and on surfaces for up to 2 hours and up to 90% of the exposed, susceptible individuals will then develop measles. So yes, we should be concerned.

Measles is one of the world’s most contagious diseases

The World Health Organization 

People born before the 1960s most likely had measles at some point and lived to tell the tale, but there were many who didn’t. Before vaccines were introduced in 1963, measles caused over 30 million cases globally and approximately 2.6 million deaths each year. Not only that, but some of those who survived had been left with life-long disabilities. Complications from measles can include hearing loss due to ear infections, febrile seizures, encephalitis, blindness due to neuritis, heart complications, Subacute sclerosing panencephalitis (SSPE) – a neurodegenerative disease, which can lead to death, and other nervous system complications. The greatest risk is among very young children, adults over the age of 20 and people with weak immune systems.

What happens when one gets measles?

Once the rubeola virus enters the body, either via the eyes or through the respiratory tract, it can replicate at the conjunctiva (membrane between the cornea and eye lids) or in the upper or lower respiratory tract respectively. The virus is able to replicate in the particular immune cells that are designed to destroy foreign particles such as viruses. More specifically, those immune cells (dendritic cells and macrophages) are responsible for engulfing foreign particles and then digesting them. The immune cells then ‘advertise’ on their cell surface, the fragments of the pathogen to other immune cells, in order to signal to the body that an intruder is present. However, in the case of measles – it is the immune cells which fall prey to the virus.

The infected immune cells travel to local lymphatic tissues, which are part of the immune system and rich in a type of white blood cells called lymphocytes. There are two primary types of lymphocytes, B cells which mature in the bone marrow and T cells, which mature in the thymus. The B cells are able to produce antibodies which are able to kill cells infected with the pathogen. T cells, depending on the type, can either kill cells infected with the pathogen, aid in the production of antibodies by B cells or send chemical signals to the rest of the immune system to heighten the immune response. The infected dendritic cells and macrophages, serve as a trojan horse, entering the lymphatic tissue and transmitting the rubeola virus to the essential T and B cells.

The infected immune cells enter the blood stream and circulate around the body infecting the skin, kidney, lung, liver as well as lymphoid organs such as the spleen and thymus. They replicate in the various types of cells, including the immune cells such as lymphocytes and macrophages, which results in immune suppression, causing individuals to be more susceptible to secondary infections by bacteria and other viruses.

Extracted from
http://www.immunopaedia.org.za/wp-content/uploads/2014/12/measles-virus-infection-cycle.jpg

Although dire sounding, the body is able, in most cases, to fight off the infection with a strong cellular immune response involving both phagocytes and the type of T cells which kill cells infected with the pathogen – even though there is immune suppression. This seemingly contradictory dynamic is called the ‘measles paradox’. Although there is a depletion of immune cells, the preferential targeting of memory lymphocytes by the virus, is what enables the body to fight back.

In a paper published in the journal, Science, the authors showed that contrary to the belief that immune suppression due to measles lasts for a short amount of time, the immune memory loss in fact lasts for 2-3 years. The consequence being that children infected with measles, are left more susceptible to other infectious diseases.

Vaccination thus does more than safeguard children against measles; it also stops other infections taking advantage of measles-induced immune damage.

Caroline Ash, senior editor of science journal

What causes the rash?

The rash, a hallmark of measles, is characterised by red, flat blotches starting on the face, spreading down the neck, torso, arms, legs, and feet, and coincides with the removal of the infection by the immune system. The activated T cells release chemicals such as histamine and nitric oxide to destroy the viruses and signals to other immune cells to come to the site. The chemicals result in inflammation including swelling and damage to normal skin cells resulting in the red and itchy rash.

Extracted from
http://www.wsfm.com.au/newsroom/urgent-measles-warning-for-visitors-to-sydney-opera-house

Vaccines are safe

Measles can be prevented with two doses of an MMR vaccine which protects against measles but also against mumps and rubella (German measles). The vaccine is approximately 97% effective in preventing measles and is safe. The most misleading and confusing material on the internet, holds that measle vaccines cause autism, life-long disabilities and death. The autism claim has been shown to be unfounded in multiple large studies – in short, vaccines do not cause autism. While, the first dose of MMR is administered around the first year of age, autism symptoms are usually only observed during the second year of life – the child was autistic prior to the vaccine; the symptoms were however difficult to detect at that early stage. However, complications due to vaccines may occur. As with any medication and vaccine, there have been adverse effects reported: including encephalitis which occurs in 1 out of 2 million – compared to the 1 in 1 000 from measles infection, Febrile seizures in 1 out of 3 000, thrombocytopenia in 1 out of 30 000 and anaphylaxis in 1 out of 1 million. Measles which is painted as a trivial disease by antivaxxers, can result in deadly complications which are more likely to occur. The CDC reported that 30% of measles cases result in complications. There is no debate on how profound the benefits of the measles vaccine are.

The risks of serious complications following measles infection are significantly greater than vaccine-related serious adverse reactions.

National Institute for Communicable Diseases

Unfortunately, in the digital world; false information is disguised as the truth, resulting in parents that have good intentions being steered toward decisions that can harm their children. The biased media focuses on the rare cases of adverse vaccine effects, fuelling fear in parents. The large media coverage on vaccines results in some believing that there must be some truth to the anti-vaxxer alarmism. The measles infection is contagious and can be deadly – vaccinating children protects them from this preventable disease.

…by the time you finish reading this, we estimate that at least 40 people – most of them children – will be infected by this fast-moving, life-threatening disease.

The UN agency chiefs

Bibliography

Belamarich, P.R., 1998. Measles and malnutrition. Pediatrics in review, 19(2): 70.

Griffin D. E. 2016. The Immune Response in Measles: Virus Control, Clearance and Protective Immunity. Viruses, 8(10): 282. DOI:10.3390/v8100282.

Griffin, D.E., Ward, B.J. & Esolen, L.M., 1994. Pathogenesis of measles virus infection: an hypothesis for altered immune responses. Journal of Infectious Diseases, 170(Supplement_1):S24-S31.

Laksono, B. M., de Vries, R. D., McQuaid, S., Duprex, W. P., & de Swart, R. L. 2016. Measles Virus Host Invasion and Pathogenesis. Viruses, 8(8):210. DOI:10.3390/v8080210.

Mina, M.J., Metcalf, C.J.E., de Swart, R.L., Osterhaus, A.D.M.E. and Grenfell, B.T., 2015. Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Science, 348(6235):694-699.

Rota, P.A, Moss, W.J., Takeda, M., de Swart, R.L., Thompson, K.M. & Goodson, J.L. 2016. Measles. Nature Reviews Disease Primers, 2:1-16. DOI: 10.1038/nrdp.2016.49.

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What is herd immunity?

Image of baby getting vaccinated, extracted from https://www.fatherly.com/news/washington-anti-vaxxers-protest-measles-vaccination/