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What’s the Difference Between Endemic, Outbreak, Epidemic, and Pandemic?

Global Health Surveillance

On Biosafety, Deadly Little Snowflakes, and Fighting Fire with Fire 

Endemic, outbreak, epidemic, and pandemic. These terms are probably familiar to you. They are also too often used interchangeably, which is unfortunate, as they have important meanings in reference to distinct levels of disease.

What’s the Difference Between Endemic, Outbreak, Epidemic, and Pandemic?

To better understand pandemics, it is important to know the differences between an endemic, an outbreak, an epidemic, and a pandemic. To begin, the endemic level of disease is considered the observed level. In the absence of intervention and assuming that the level is not high enough to deplete the pool of susceptible persons, the disease may continue to occur at this level indefinitely. Thus, the baseline level is often regarded as the expected level of the disease. Diseases we might think of in this category could include the common cold, which is almost always circulating in a community. It also includes malaria, which is endemic in parts of the global south, with Africa carrying “a disproportionately high share of the global malaria burden.”

An outbreak occurs when there is a sudden rise in the number of cases of a disease, but is limited to a specific geographic area. An example of an outbreak is the increased number of dengue cases seen in Central and South America, Mexico, and the Caribbean earlier this year, which prompted a travel notice

An epidemic can occur when an agent and susceptible hosts are present in adequate numbers, and the agent can be effectively conveyed from a source to the susceptible hosts. This occurs in a broader geographic area than an outbreak, such as a community or region. One example of an epidemic is the 2003 severe acute respiratory syndrome (SARS) epidemic, which made more than 8,000 people worldwide sick and killed nearly 800 in more than two dozen countries. 

A pandemic then refers to an epidemic that has spread over several countries or continents, usually affecting a large number of people. Unfortunately, we’re all too familiar with a pandemic, having experienced COVID-19. First discovered in Wuhan, China in late 2019, the SARS-CoV-2 virus had made its way to Washington state and much of Europe as an epidemic by January 2020, and cases continued to increase exponentially to eventually spread nationwide and globally by early spring 2020. In March of that year, the World Health Organization (WHO) officially declared the COVID-19 outbreak a pandemic.

Before COVID-19, Were There Pandemics?

Throughout history, infectious diseases have impacted how humans live… and die. Though the word “pandemic” was first used in the year 1666, “the concept of a pandemic, i.e., of a disease which could affect all the population of the world, came into shape as the 1889 influenza pandemic appeared and spread worldwide.” An increasing global population and global travel made this possible. 

The 1918-1919 influenza (H1N1) pandemic could be the most well-known of recent pandemics, due in part to its profound mortality rate, “causing up to 50 million deaths, including some 675,000 deaths in the United States alone.” 

Since then, the 1957-58 influenza (H2N2) pandemic most dramatically impacted Southeast Asia, with deaths estimated to be “1.1 million worldwide and 116,000 in the United States.” The 1968-69 influenza (H3N2) is believed to have originated in China and had a similar impact, killing “1 million worldwide and about 100,000 in the United States.” 

Most recently was the 2009 influenza (H1N1) pandemic (a.k.a. “swine flu,” as it is believed to have originated in pigs), which was different than previous pandemics because of the human population it impacted and by being less severe. This flu primarily affected children and young and middle-aged adults, whereas previous pandemics had more dramatically impacted populations over the age of 65. 

Today, weather extremes resulting from climate change are driving increased incidence of infectious diseases. Studies provide evidence that climate change has contributed to the expanded range of ticks and mosquitoes, with these disease vectors potentially increasing their range by hundreds of miles over many generations. As they spread, they expand the geographical distribution of the new and emerging vector-borne diseases they carry with them. This increased range makes vector-borne diseases like dengue fever, malaria, Zika virus, Rocky Mountain spotted fever, tularemia, and others an emerging threat to the health of human and wildlife populations. These changes may increase the chance that one of these diseases or something yet unknown will become the next pandemic. 

When Working with Viruses, Biosafety Is Key

Our research scientists work with viruses in laboratories with different biosafety levels, depending on the risks to humans or animals. When working with a virus like porcine reproductive and respiratory syndrome virus (PRRSV), which is highly contagious in pigs and causes disease in their herds, we do so in a BSL-2 laboratory. When working with SARS-CoV-2, the virus that causes COVID-19 in humans, we do so in a BSL-3 laboratory. For additional insight into BSL laboratories and the safety measures involved, read “Biosafety 101: Understanding Laboratory Biosafety Levels.” 

Because of the increased risk associated with SARS-CoV-2, additional safety precautions are taken by laboratory staff, the procedures used, and even in the construction of the laboratory itself. For instance, security measures permit only cleared personnel into any of these laboratories, with BSL-3 being especially restrictive. In these laboratories, research scientists must wear dedicated clothing and personal protective equipment and follow very specific decontamination procedures of the laboratories and its equipment. These practices ensure the safety of our researchers and staff, as well as the quality of the work being conducted in the laboratories. 

Deadly Little Snowflakes

People often think of a virus being literally just “a” virus, but what they don’t know is that there can be billions of viruses in just 1 cm3 of tissue. Our Dr. Luca Popescu calls them “deadly little snowflakes” because each of them is different. Each also possesses the ability to mutate at a very rapid rate and reproduce in huge quantities. Viruses like PPRSV and SARS-CoV-2 are both highly mutagenic, meaning they have the ability to mutate and take on new characteristics, which leads to new variant strains. These new strains may possess characteristics like greater virulence, higher mortality, and different symptoms expressed by the diseased individual than with past variants. As these viruses mutate, antibodies and adaptive mechanisms are not as good at recognizing them and supporting an effective immune system response, as we saw with SARS-CoV-2. Through mutation, each variant of that virus was slightly different, which is why they impacted infected individuals differently. 

In Dr. Popescu’s past work with PPRSV, he found that some pigs could effectively neutralize the virus after becoming infected. Most pigs display minimal disease signs from PRRSV because their bodies develop a sufficiently strong immune response that keeps them from getting the worst of the symptoms. However, this does not prevent the virus from spreading in the herd. As the virus spreads from pig to pig, it will continue to mutate, picking up new characteristics that allow it to keep escaping complete neutralization and thereby keep spreading. This is why vaccines that are longer-lasting and offer greater breadth of protection are necessary. At MRIGlobal, we are responsible for helping to build next generation therapeutics and vaccines. 

Messenger RNA Fights Fire with Fire

The use of messenger RNA (mRNA) is the next generation. A naturally-occurring molecule in the body’s cells, mRNA carries genetic information from DNA to create various proteins and drive cell functions. When infected with SARS-CoV-2, the virus hijacks this cell machinery to make more virus, which then overwhelms the immune system and makes us sick. Scientists have borrowed from this approach when designing vaccines to combat the virus—using it to fight fire with fire—or mRNA with mRNA. 

When dosed with an mRNA vaccine, the mRNA gets taken up by your cells and instructs them to create spike proteins, which are also found in the SARS-CoV-2 virus. The body recognizes these proteins as foreign and creates antibodies to fight against them. Because the body’s immune system is then familiar with these spike proteins in the vaccine and how to fight against them, it is primed for doing so when encountered with the real virus. 

As the virus replicates, it doesn’t always make exact copies of itself (it doesn’t proofread), which leads to genetic mutations. Sometimes, the virus will mutate enough that the body no longer recognizes it, escaping the body’s immune response prompted by the vaccine. This results in the many COVID variants you have heard about—Beta, Delta, Gamma, Omicron, and others—in the past few years. 

To learn more about mRNA, we spoke with Dr. Luca Popescu, an MRIGlobal veterinarian turned global infectious disease expert. His experience includes working with viral and bacterial pathogens like anthrax, influenza, tularemia, and SARS-CoV-2. You can hear more from him on the history of mRNA vaccines, why they’ve been so critically important to the COVID response, and what’s next for their use in supporting global health on this episode of MRIGlobal’s “Science Diction” podcast.


Contact MRIGlobal to further understand our work in infectious diseases. We offer a broad portfolio of infectious disease testing assays and capabilities across diagnostic disciplines, from screening and diagnosis to genotyping, therapy, and monitoring. Those seeking analysis of infectious disease tests can trust in our breadth of experience and knowledge – not just on the subject matter, but FDA protocols as well. 

To learn more about the work we’ve done or how we can help you, contact us today. If you are part of an agency, business, or academic institution seeking assistance with a project, use our Project Quote Tool to get started. 


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