The Polio Virus - Close To Eradication?

Also known as Poliomyelitis, polio is an infectious disease, caused by the poliovirus. Infection can result in infantile paralysis and muscle spasms in its worse cases. The virus can be ingested through contaminated food or water, and be absorbed through the gut wall. From here it is able to move to the spinal cord and paralyse its nerves.

Above: Scanning Electron Micrograph of the poliovirus (Source: Polioeradication.org)

Typically, polio is relatively prominent in developing countries, Asia containing most of the transmission. Evidence suggests that the poliovirus has been around for a very long time, some sources quoting that it infected people in the prehistoric ages. However up until the 20th century, major epidemics were simply unknown. Until this time, the virus spread was known to be endemic - this means that in an area, the virus' transmission remained fairly constant, with no real surges in infection. In the 20th century however, Europe, followed by the Americas began to experience widespread epidemic of the disease. What is interesting is that the disease saw its highest incidence in the summer months of each year.

'At its peak in the 1940s and 1950s, polio would paralyse or kill over half a million people worldwide every year' (Wikipedia).  Franklin D. Roosevelt was one of the most notable people to be infected with the poliovirus, becoming permanently paralysed from the waist and down. (However this seems quite an unusual case as the poliovirus is typically known to induce infantile paralysis. Therefore, there is debate surrounding this specific case) This is a staggering number, considering that the rates of transmission were 'controlled' only couple of decades before this period. These rather catastrophic events initiated a global medical response, with research funding increasing dramatically.

Probably one of the most known national crises with polio was the Copenhagen polio epidemic in 1952. However epidemics of equal magnitude were spreading across America at the time.

"Anyone wandering in to Ward 19 of Copenhagen's Blegdas Hospital in the autumn of 1952 would have been confronted by an extraordinary sight. In each of the seventy beds arranged in two straight lines lay a child paralysed with polio with a hollow plastic tube inserted into the trachea through a cut in the neck - a tracheostomy - to which was attached another long piece of tubing, at the end of which was a rubber bag. Next to each bed sat a young medical student who, every few seconds, would squeeze the bag, blowing oxygen through the tubing into the child's lungs and then letting go, repeating this action for six hours at a stretch[...]According to Ann Isberg, one of the children, 'it was not a sad time', rather 'like [during the] war there was a spirit of resistance - everybody was doing their best'."

 - An account describing the atmosphere in a hospital ward, housing polio patients, from 'The Rise and Fall of Modern Medicine' written by James Le Fanu, M.D. 

Special respiratory centres were then established in the Blegdas Hospital, under the initial influence of anaesthetist Bjørn Ibsen, in order to help ventilate the polio patients (whose breathing was compromised by paralysis). This was essentially the birth of intensive care. Following these events, which constituted several 'summer plagues', in 1957, Jonas Salk, an American researcher helped synthesise the first successful polio vaccine. Choosing not to patent it, he allowed the vaccine to be distributed all over the world for free. This led to a vast decline in polio cases. By the late 1980s, many described the virus 'being close to eradication' in most countries.

Above: Polio ward in Hynes Memorial Hospital in Boston, 1955 (Source: Dailymail)

Above: An Iron Lung machine, used in the assistance of ventilation/breathing in polio patients (Source: Centers for Disease Control and Prevention's Public Health Image Library (PHIL) - via Wikipedia) 

Here is one staggering statistic: 'Polio cases have decreased by over 99% since 1988, from an 
estimated 350 000 cases then, to 416 reported cases in 2013' (The World Health Organisation Polio Fact Sheet)

Despite this, new cases of polio have been emerging in Afghanistan, Pakistan and Nigeria. In 2014, the World Health Organisation saw that this surge in cases meant the declaration of a public health emergency of international concern (PHEIC). The vital key to eradicating polio completely is nationwide herd vaccinations, as the virus cannot survive for long outside a host.

The Final Stages in Eradicating Polio

As of early 2015, scientists have been collaborating internationally in order to develop a synthetic vaccine in the hope of eradicating the last remaining strain of the poliovirus. Together, the World Health Organisation and the Bill & Melinda Gates Foundation have provided a $674,000 (£438,000) grant to fund the research. The main problem with current vaccines is that because they utilise the weakened (attenuated) form of the virus, in some patients, this may initiate an immune response. This would mean that the virus can be 'reactivated' and passed on to those that have not been vaccinated. However a synthetic vaccine means no genetic material which essentially indicates that the vaccine contains no virus.


We are extremely close to eradicating the poliovirus off the face of the Earth. What a human feat that would be.


References

In addition to sources given above:
- Credit to the World Health Organisation for their information and data on the poliovirus and the polio vaccinations
- Additional Credit to BBC Science Correspondent, Jonathan Amos for his article on the new synthetic vaccine for polio, 'Synthetic vaccine sought to finally eradicate polio' (14th February 2015) Read more.
- Additional Credit to James Le Fanu's 'The Rise and Fall of Modern Medicine' which features the events surrounding the Copenhagen polio epidemic and the birth of intensive care.

Hepatitis C - Can We Use Genetics To Find Effective Treatments?

As devastating as viral infections go, Hepatitis C is one of the most severe, in worst cases leading to cirrhosis - liver tissue scarring. There have been cases where individuals have developed cancer as a result of the destruction due to the Hepatitis C virus. The success of the Hepatitis C virus is largely due to the survival of its most deadliest strains. The fact that humans are the only species as far as we know that can be infected with HCV makes us somewhat more vulnerable. What is more interesting is that despite all our current knowledge on viral replication and adaptation, the mechanism of this virus infiltrating cells and causing damage is not fully understood. You could argue this 'void' in our scientific knowledge is preventing us from devising effective treatments, not only to this particular type of infection, but others too. However just like any other virus strain, the Hepatitis C strain which causes disease does utilise the host cells 'machinery' in order to replicate itself multiple times. It follows that whole new virions are produced from the newly synthesised viral protein. Despite there being some individuals who are able to fight off the virus, most people develop a chronic infection which can last as long as a lifetime. Continued degrading of the liver over a prolonged period means that eventually the liver cells lose function -  only a liver transplant can save the life of the patient.

What seems reassuring statistically, is that according to the World Health Organisation, around 3% of people worldwide are affected severely by the Hepatitis C virus (HCV). A small percentage one may consider, however it equates to a very large quantity. Additionally, a large number of people may have not been diagnosed with the infection as the infection takes time to develop. This can only mean that the actual number of people affected chronically with HCV is much higher.

A Summary of HCV Transmission:

A blood-bourne infection, HCV is commonly transmitted through (vascular) medical operations, or through intravenous drug usage. There have been nationwide catastrophes in some countries where blood, contaminated by HCV, has been used for transfusions. The identification of the virus was too late, and many people were medically affected.

The origin of the spread of HCV is largely unknown, although many agree that it could have been initially spread by some kind of vector, a mosquito being a predictable example. It has been discovered that the virus can spread through sexual transmission, however blood-to-blood contact is seen as the most efficient method of the virus' transmission.

Above: Electron Micrograph of the Hepatits C Virus (HCV) isolated from cell culture (Wikipedia)

The Significance of the Viral Genome:

The HCV, as characteristic of many viruses, is able to mutate at a frequent rate, making it very difficult to develop a long-lasting vaccine. The length of its genome is relatively short at around 10000 nucleotides long. The primary reason for the rapid mutating of the HCV genome, is that unlike in humans, the HCV virus has no mechanisms in place to proof-read its own DNA. This frequency results in copying errors during the process of DNA replication. Combining this feature (or rather a lack of it), with HCV's ability to replicate at an extraordinary rate, results in many mutations in the viral DNA sequence.

To most people, a mutation is seen an event detrimental to the host organisms, however this isn't always the case. In viruses, due to the large number of mutations that occur, mutations can sometimes be advantageous. Therefore the virus is able to acquire a protein that serves valuable to virus, allowing it to survive in more extreme conditions. One application of this is that an advantageous mutation can cause a virus to the evade the host organism's immune response. The host's own cells may recognise the new viral proteins as 'self' and thus fail to identify the intruder.

As mentioned, the HCV constitutes many different strains, and there is scientific evidence of this. Comparing HCV genomes from around the world, where it has caused infection in the local population, has given scientists insight into the impressive genetic diversity of this virus. Such diversity is simply uncharacteristic of most organisms, take humans as an example: 'the difference between the DNA sequences of individual humans is less than 1%'. However no matter how genetically diverse the HCV is, liver disease still developed upon infection.

Scientists have managed to categorise the differences between HCV strains, and classify the different HCV genotypes. The seven major genotypes of HCV range from G1 to G7. Each strain is prominent in different areas of the globe:

• G1 - found in Africa (endemic - constant transmission rates) as well as parts of Europe, the USA and Japan (causes epidemics - greatly fluctuating transmission rates).
• G2 - found in  Western Africa (endemic) and near Mexico
• G3 - found in Asia (endemic) - in and around Northern India
• G4 - found in (Central) Africa (endemic) 
• G5 - found in (southern) Africa (endemic)
• G6 - found in (Eastern) Asia (endemic)
• G7 - found in (Central) Africa

Above: World map showing the distribution of various strains of HCV and relative proportions of different genome types in each area (Hepatitis C Education & Prevention Society)

What is intriguing is that worldwide medical data suggests that some strains of HCV are statistically easier to treat than others. Take G1 and G2 as examples. G1 is in fact the most common type of HCV in the UK and is notoriously difficult to eradicate, 'only 50% of G1-infected people are treated successfully'. However G2 induced Hepatitis seems easier to treat, with success rates as high as 80%.

Looking to the Future:

Recent developments in genome sequencing, drug synthesis and virology has enabled scientists to develop potential drugs to combat this deadly virus. In today's world however the HCV isn't the only significant threat to global health, with HIV/AIDS being a notable contender. The primary function of these new drugs is to inhibit particular stages of the viral life cycle, by targeting viral enzymes. This is a more virus-directed approach which contrasts greatly to old drugs, which only focused on increasing the strength and effectiveness of the host's immune system. Additionally, knowing the differences in the genotype between strains of HCV will enable scientists to develop drugs capable of destroying all strains in equal effectiveness.

So who will win this 'evolutionary arms race'?

References:

Credit to Dr Rebecca Gray PhD, who is studying the evolution of HCV and is now a research fellow at the University of Oxford for her original article on Hepatitis C published in the Biological Sciences Review (Volume 26, Number 1).

Additional credit - 'Hepatitis C - NHS Choices'. Read more.
(Image references are given in captions)

Further reading:
 - The World Health Organisation provides more information on the Hepatitis C Virus. Read more