Smallpox, from first outbreak to elimination

Inhoud Inleiding Het pokkenvirus, wat maakt het gevaarlijk, hoe werkt het op moleculair niveau The first clusters Over de CDC en haar rol in smallpoxuitroeiing Het vaccin, hoe is t bedacht door wie en hoe werkt het in op moleculaire processen in je

lichaam The road to elimination

De CDC en haar rol hierin Waarom wordt het nog in laboratoria onderzocht? Smallpox virus retention controversy

Introduction

I’m going to try to tell you of one of the greatest success stories in medicine, the eradication of smallpox. I first learnt about this disease at a camp I attended this summer. This camp wasn’t just your usual summercamp, it was a ‘Disease Detective Camp’, organized by the CDC. So I found myself flying to Atlanta, all by myself, to spend a week between 30 American peers, all with the same interest in public health. And on top of that thousands of CDC employees, of which we obviously only met a certain number, but who were all extremely kind, helpful and supportive. Let me start by briefly explaining what kind of organization the CDC is.

The CDC is short for the Centers for Disease Control and Prevention and is a large federal organization that plays a fundamental/important role in public health. They carry the responsibility for the health of all US-citizens in the case of a multi-state disease-outbreak. As a federal organization they are to refrain from interfering in a single-state outbreak, according to the Tenth Amendment to the United States Constitution.Their staff consists of 15,000 employees and their headquarters are situated in Atlanta. They focus on many public health fields, some of which are infectious disease, foodborne disease and environmental health. They also provide information on non-infectious diseases and undertake action in the case of emergency outbreaks in the US. They serve more or less as a big source of reliable information and as a major research organization regarding health. On top of that they also play a significant role in Global Health. During my camp I was able to speak with many CDC-employees of which some worked at the Global Health-department. They had tremendously interesting stories concerning their adventures about travelling to foreign, mostly third-world countries, in an effort to minimize infections of certain diseases.This is also how the CDC played a major role in the eradication of smallpox. This subject really caught my attention and as the CDC had been so significant in the eradication-process, they had a lot of interesting information available for us.

WHO magazin World Health declares one of the greatest triumphs of medicine

This first cases of smallpox supposedly occurred thousands of years ago, scars were found on Egyptian mummies. The fact that smallpox is now eradicated and non-existent is almost inconceivable when thinking of how many people must have suffered with the burden of having this disease. It made me realize how we should take the eradication of smallpox as an example and try our best to follow the same strategy on other significant infectious diseases. I decided that it would be interesting to dive into the process smallpox underwent, and to investigate this disease, from its first clusters, all the way through understanding the virus, the invention of the vaccine until the very last case.

The diseaseSmallpox is a disease caused by one of two viruses, Variola major or Variola minor. Variola major was a lot more common than Variola minor, it also was a lot more fatal. V. major had a mortality rate between 30-35 per cent. As opposed to V. minor, with death rates historically of 1% or less.

SymptomsOnce infected with the Variola major a incubation period of 7-17 days follows. Most typically the incubation period ranges from 12-14 days. During the incubation period the infected person is not yet contagious, after this period the first symptoms start to show.

The first phase is called prodrome and takes 2-4 days, the infected person can be contagious during this period, however not by far as contagious as the period following the first rash.During the prodrome phase the initial symptoms start to occur, including high fever (38-40 degrees Celsius), head and body aches, overall discomfort, severe back pain and sometimes even vomiting.

Following the the prodrome phase an early rash onset occurs, this period takes around 4 days, during which the person is most contagious. Image 1 shows the rash distribution of smallpox

compared to that of chickenpox. First the rash emerges as small red dots on the tongue and in the mouth. After the rash has developed into sores, they burst open resulting in a large spread of the virus in the throat and mouth, at this moment the person is incredibly contagious, as the virus can now be easily spread through face-to-face contact. Around the moment the sores break down in the mouth, a rash emerges over the skin of the body and face, the rash usually spreads over the entire body within 24 hours. After three days this rash turns into little bumps. By the fourth day theseabscesses are filled with a thick liquid and pus, they also have a depression in the center, which makes the bump easily identifiable as a smallpox-abscess.

After approximately a week since the symptoms first started, the bumps start to turn into pustules, meaning that they become more sharply raised and very firm. The infected person is still very contagious, but not as severe as before.

After about five days, these pustules start to form a crust, thus turning into a scab. Five days later nearly all of the sores have turned into scabs.

During the next six days the scabs begin to fall off the skin. Usually three weeks after the first appearance of the rash, every scab has fallen off. When the scab falls off the skin, the location of the scab is marked by eventually turning into a pitted scar. Thus leaving a person behind with a fully scarred face and body.

The infected person remains contagious until every single scab has fallen off, so the period in which a person is contagious is as long as approximately three weeks.

Image … overview of the developments of bumps

Image 1: rash distribution

Variola major (image 2) has 4 subtypes: Ordinary smallpox, the ordinary form of smallpox which accounts for 90% of the cases. Modified smallpox, this is a more mild form of smallpox which develops in people who

were previously vaccinated. Malignant (flat) smallpox, this is a type of smallpox in which the lesions did not develop

into pustules on the skin, but the lesions remained under the skin. The variety of smallpox was very severe.

Hemorrhagic (fulminant) smallpox is a very rare but very severe form of smallpox. Many small hemorrhages under the skin cause the skin to turn deep purple. The fatality rate was near 100%.

Image 2: Variola major structure

What happens inside the bodyThe virus enters the body through inhalation, which makes it a highly contagious disease. So it is either spread through face-to-face contact or through a fomite, which is a nonliving object that is contaminated by the virus. When the virus has been inhaled it rapidly advances to the nearest lymph nodes. 3th-4th day: the virus enters the blood and spreads to the bone marrow and other lymph nodes.

VaccineThe invention of the vaccine against smallpox was, of course, a significant link in the long chain to the eradication of the disease.

The period of time between the very first observation which was the foundation for the vaccine (1796), and the invention of the vaccine as it is known today (1960), is almost 200 years.During those years the vaccine has been subject to an incredible development process

In this chapter I will try to explain as elaborately as is possible with my knowledge, what this evolvement looked like.

Edward JennerWhile observing milkmaids, Edward Jenner’s attention was attracted to the fact that those, who had earlier been infected by cowpox, would not become ill when exposed to smallpox. Using the method seen in image ... , he started inoculating individuals with cowpox, to ensure immunity against smallpox.

Image … , How Edward Jenner ensured smallpox immunity

EradicationThe eradication of smallpox has been a fact since 1980, I myself have grown up without the constant fear of obtaining this disease, unlike many others before me. Thousands of years the fear of being infected by variola was a never-ending concern. For me it seems far away, but it fascinates me how big a role this disease used to play in everyday life, that is why I think it’s so interesting to look at how this disease was finally eradicated, after thousands of years of trouble.

Before I start describing how smallpox was eradicated, we have to understand what the difference between elimination and eradication is.

When speaking of elimination, we are looking at a defined geographical area, so for instance a country or state. The number of new cases has to be zero (or another low number) in this defined geographical zone for a certain period of time, usually a year, for a disease to be eliminated.When a disease is established to be eliminated, further measures still have to be taken. The disease has not yet disappeared forever, the cases in a certain country or continent are simply very low, but this does not exclude a new outbreak.

Eradication, however, is when, for a period of three years, there has not been a single case reported in the entire world. When a disease has been eradicated no further measures have to be taken, because the disease does no longer form a threat to mankind and any form of outbreak can now be excluded.

The eradication of smallpox was the result of a vaccination programme which was set up in 1967 and organized by the WHO (World Health Organization).

Image …, Promotional poster eradication smallpox

List of sources https://emergency.cdc.gov/agent/smallpox/overview/disease-facts.asp https://microbewiki.kenyon.edu/index.php/Smallpox_Virus https://en.wikipedia.org/wiki/Lymph_node https://en.wikipedia.org/wiki/Smallpox https://www.emergency.cdc.gov/agent/smallpox/vaccination/facts.asp http://emedicine.medscape.com/article/237229-overview http://www.healthline.com/health/smallpox#Symptoms2 http://www.mayoclinic.org/diseases-conditions/smallpox/basics/symptoms/con-20022769 https://www.bcm.edu/departments/molecular-virology-and-microbiology/emerging-

infections-and-biodefense/smallpox-virus