The Viruses

[PLAYING MUSIC]

OLAKUNLE ALONGE: So here we’re going to be talking about some basic facts around polio as a disease-causing agent; poliomyelitis, the disease that the polio virus causes; and the polio eradication initiative. Here you see the micrograph of the polio virus, which is a single-stranded RNA, so basically the virus is the genetic material [INAUDIBLE] RNA material itself. But it belongs to the family of the [INAUDIBLE] family of the enteroviruses and to the other types of enteroviruses. And “entero,” meaning mounts and the GI tract, so those viruses are transmittable through the ingestion of contaminated food and water.

And this is really important to understand as we begin to think about the biology because it’s an organic virus, it’s really– in the process of transcription, it’s a lot less stable compared to a DNA virus. So what happens is that you could have passage of a mutation is actually high, and it has implications for the stability of the vaccines that are derived for the virus and also on the virulence in terms of how harmful the virus is as [? it’s ?] transmit or replicate over time. So let’s talk a little bit more about the viruses. So as I said earlier on, the polio virus, it’s an RNA virus and there are three major strains.

The strains are distinguish based on their genetic properties, so they are distinguishable in terms of their having a basis within each of their different types of RNA. So you have the wild polio type 1, which is often regarded as the most virulent. [? Its ?] status, currently endemic– in fact, it’s the only still-occuring wild polio virus that we have in the world. It’s endemic in Afghanistan and in Pakistan. And the other type 2, which is the least virulent– and this has been eradicated. This incidence of this is completely zero across the globe. It was last detected in India in 1999. And then we have the wild poliovirus type 3 which was declared eradicated in 2019.

So again, there are genetic materials that are different between each of these different substrate, and that actually qualifies the differences in the virulence, comparing one strain to another. Like I said earlier on, these viruses are transmitted through the fecal-oral route. So that is to say that they are found in contaminated– so when somebody who carries the virus, when they ingest or when sanitary measures are not put in place for toilets and so on, they can contaminate water sources and food supply. And then when an uninfected person ingests the water or the food, the virus lodge within the gastrointestinal tract, that is to say the stomach, the intestine, [INAUDIBLE] intestine, the small intestine, the large intestine, of the individual.

And the virus uses the machinery for replication, forms the host, and continues to propagate itself and multiply. So the individual sheds viruses when they ingest. And at the same time, the virus come from the intestinal tract going to the bloodstream. And then from the bloodstream, the virus goes into the nerves, which are the areas that are mostly affected. And so from the nerves, the virus usually travels to the spinal cord where the nerves originate from and destroys the motor neuron, that is, the nerves that controls the skeletal muscles within the spinal cord. And that’s why you have your paralysis.

So you can see that based on the transmission of the virus, you can begin to understand what some of the clinical manifestations can be. Because the viruses replicates in the intestine, you could have some gastrointestinal symptoms including vomiting and upset when somebody is infected with the virus. Because the viruses affects the nerves and it affects the motor neuron that control the nerves, you could have irritation of the spinal cord, which presents as meningitis or meninges [INAUDIBLE].. And you could also have paralysis when there is affectation of the anterior motor neuron.

So I’ll say again, the transmission routes for the virus, or the transmission of the virus and the routes that the virus takes within the human body, can actually shed light on to the clinical manifestation of the virus. Now, one of the cardinal criteria for eradication is that humans supposedly should be the only reservoir for the virus. And this applies to polio, that is to say that humans are the only susceptible host to the virus. I mean this is as of the time when the Eradication Initiative would have been set. and the virus only replicates in the host.

But in recent times, we know that there are signs that maybe perhaps, just yet uncertain, the virus may actually amplify in the environment, even outside of humans. But again, based on the biology, we know that humans are the only reservoir. So that is to say that if you were able to eliminate the incidents among humans, we would eliminate the virus from the face of the earth. Back to the clinical manifestation, as I described earlier on, the virus is really replicates in the intestine, and from the intestine, gets into the bloodstream. Some from there travels through the nerve to get to the spinal cord, and then infects the motor neuron cells within the spinal cord.

But this is really weird, because indeed, in 99% of infection, we do not see any paralysis. In fact, in about 74% of people that are infected, there is no upper end symptoms or signs. There is nothing to suggest that they are infected with the polio. And this is really important because this is some of the things that present challenges for eradication. So for you to eradicate a disease, it’s a lot easier if you can see when somebody is infected with the disease, so that we know and you’re able to identify cases. You’re able to isolate, quarantine, and so on. But in this case, it’s an upper end disease in the vast majority that are infected.

And in about 24% of cases, you have some very mild, very mild [INAUDIBLE] typical of any viral infection, so for instance, when you have stomach upset, vomiting, muscle pain, headache, and so on. So this usually sets in between one to five days after the individual himself is infected. So in majority of cases, you see that the disease is in upper end but with no clinical manifestation. And in some cases, it present as very mild viral illness. So it’s only in the very rare occasion, so it’s only in less than 1%, that you’ll have paralysis.

In fact, paralysis due to the wild poliovirus has been said to occur only in between one out of 100 to one out of 500 individuals that are infected. When paralysis do occur, paralysis do occur. I mean it obviously affects the skeletal muscles given that the virus infects the anterior motor neuron cells. And so it affects the muscles that are voluntary, this voluntary skeletal muscles. So for instance, muscles of the limbs, muscles for breathing and swallowing and chewing. So it can affect both the muscles that control the limbs and also affects the cranial nerves that controls swallowing and so on. And usually, the lower limbs is more affected when there’s paralysis, more than the upper limb.

And you have affectation on the proximal muscles more than the distal muscles. So for instance, the thigh is going to be more affected than the muscles that are farther away from the spinal cord. And then in cases where it affects the cranial nerves that controls breathing, that’s where you have the bulbar polio which can lead to respiratory failure because of the inability to do it. So like I said again, [INAUDIBLE] paralysis, are indeed very rare. It’s a cause in between one in 100 cases to one in 500 cases. But it’s so true that the [? effects ?] of the disease is really scary, because where you see the paralysis, it really evokes a lot of terror or fear.

And in cases that paralysis do occur, the paralysis usually sets in within five days of the infection. And usually, if there’s ever going to be any recovery, the recovery would have happened by the end of the month or so. So most paralysis is permanent. That is not to say that patients don’t continue to recover over many months, but we know that whatever recovery that would have happened usually typically happens within the first [? two ?] month. Again, when you have the paralysis, it’s called acute flaccid paralysis because it’s acute, because it’s rapid onset. It occurs within five days of infection. It’s flaccid because there’s complete weakness of the skeletal muscles that are used for voluntary action.

But again, to clarify, that is really– it’s a vehement manifestation of polio, so many more people who have polio don’t have the manifestation of the paralysis. Again, this is a very highly resolute picture of the poliovirus. So you see, it’s really interwoven with RNA [? –I know– ?] and kind of interwoven into themselves. Inside of this is really what holds information for replication and acquires, admits the host particles in order to replicate itself. The history of polio, it’s been since the ancient times, actually. So we know that even as far back as India in the early BCs that– the hieroglyphics from the Egyptians really just show [?

affectation ?] of polio even in Egypt, even among the pharaohs of Egypt, way back. And we recognize that the onset of polio as an epidemic began to be more noticeable even as sanitation improves around the world. So from the 1700s to the 1800s, as societies were becoming more affluent, given that the polio is well-linked to unsanitary conditions, and people were more at risk because of trying to provide sanitary condition. Or within the environment, we have pockets of places where unsanitary conditions allow some propagation. So you have a scenario where people are not widely as exposed to poliovirus as it used to be, when conditions were likely broadly unsanitary for most populations, so everybody is exposed.

So we really have people developing immunity in some ways to that. So as society began to advance, and prosper, and begin to put in measures for cleaning [? hands, ?] for sanitary, for making sure that vomit is clean, there is less natural exposure to the poliovirus, and therefore that increased the risk of epidemics. And that’s what we began to see in the United States and in other parts of the world in the 1700s and the 1800s, by which time it was really scary because parents see children were OK, and then suddenly, they couldn’t walk. In some cases, some children had bulbar polio which affected breathing. And there was a lot of morbidity and mortality.

So there was a lot of scare. By the early 1900s, good attention was brought to the polio by the infection of Franklin Roosevelt. One of the US president was infected as an adult at the age of 39. So in the 1920s, that really brought a lot of attention to the polio program. And he also let people just see the disease from a different perspective and also facilitated and led a discussion on resources and collaboration. So by the 1950s, vaccines and injectable vaccines was developed by Salk, which really helped to reduce the epidemics of polio in the United States drastically. And then in 1963, or thereabouts, the oral polio vaccine was developed by Sabin.

And this even further helped the elimination of poliovirus outside of the US, where it was still a very big issue. And given the nature of the OPV, Oral Poliovirus, it could be delivered readily through the mouth, so that facilitated mass use, mass immunization. And the development of both of these vaccines really aided or paved the way for discussion around the Global Polio Eradication Initiative. So with the success with vaccination– with injectable –in the United States earlier on and with the Europe polio vaccine globally, in some parts of the world, [INAUDIBLE] and [INAUDIBLE] came together in 1988 recognizing that there is an effective vaccine. And there’s enough commitment to seek eradication of polio from the world.

So again, a lot of the sources are there for you to pull from in terms of the history of polio and how it has evolved and shaped human society over these years. This is just to show you some of the early reports of poliomyelitis in the early 1900s. We see instances where we had rapid epidemic of the poliovirus, and then as people began to know the disease, understand its biology, the way it transmits in the environment, and sanitary conditions were put in place. It was helping with the epidemics to some extent but at the same time putting more people at risk. As vaccines [INAUDIBLE] to develop vaccines were later discovered, it drastically reduced the incidents of the poliomyelitis cases.

So again, you see the graph, you see its rapid rise because of the epidemic. And then it decline as a result of public health measures, which largely around sanitary and [INAUDIBLE] sanitary conditions. And then much later on, use of vaccination really helped. In low-income, settings the disease is endemic. And as of 2019, we know that the diseases are endemic largely in Afghanistan, which is the map that you see here, and in Pakistan. I would note that majority of the people that are affected are infants and young children. So you have, for instance, in Afghanistan, as of October 2019, you have your total cases of wild poliovirus of about 20 children.

And we [INAUDIBLE] looking at not just only the children, but also looking at samples from the environment, basically taking sewer samples. And also showed positivity in specific areas within Afghanistan, where the samples tested positive for the poliovirus. Here, we also see somewhat of a snapshot of the extent of vaccination and the people that are involved in the vaccination. Many of them are females, and so on. So this is really to show to you, in places where the disease is still endemic, there’s a lot of ongoing efforts to eliminate the disease from those areas and then to eradicate the disease globally. And this effort really required a lot of concerted activity of the large swaths of stakeholders at different level.