Viruses aren’t automatically your enemy. These ambiguous, definition-bucking little beasties, found in every single environment on Earth, play a variety of roles – and the ancient precursor to one seems to play a role in how we form memories. Saying that, plenty of viruses can cause lethal infections in humans, with some being deadlier than others. Without a doubt, influenza is the single biggest killer of them all. Back in 1918, between 50 and 100 million people died after being infected by the virus, which was around 5 percent of the planet’s population at the time. Overall, half a billion people were infected. Far from taking the lives of those that were otherwise vulnerable – the already sick, the elderly, or the very young – it spared no one. There are several myths surrounding the pandemic, but it’s safe to say that it was the deadliest mass infection in human history. In fact, it’s something that plenty, including Bill Gates, have warned could happen again if we take our eye off the ball, or if we defund key agencies tasked with keeping the wolf from the door. By total number of deaths, there’s no competition: The H1N1 strain of influenza virus is by far and away the most lethal in this respect. What if, though, we look at the mortality rate of viral infections instead – the number of infected people that ultimately die? At a rough estimate, based on the high-end deaths value, H1N1’s case fatality rate (CFR) back then was roughly 20 percent. As it turns out, there are viruses that have frighteningly higher CFRs out there in the world today. Take rabies, for example. This is a disease that, according to the World Health Organization (WHO), occurs in more than 150 countries around the world. It’s present on every single continent, except Antarctica, and 99 percent of human transmissions occur through dog bites. Children aged between 5 and 14 years are the most frequent victims. Different variants have different incubation periods and epidemiologies. Those with “furious rabies” can become hyperactive and develop a fear of water and sometimes fresh air. A few days later, cardiorespiratory arrest occurs. Those with paralytic rabies take longer to die. It begins to immobilize your muscles at the bite point, and eventually you fall into a coma and die as your brain and spinal cord continually inflame. Elke Muhlberger, an associate professor of microbiology at Boston University, told LiveScience that without treatment, rabies is 100 percent fatal. It is, however, vaccine-preventable, via the inoculation of dogs. There are also treatments available for humans to have in case they get bitten. In fact, every single year, more than 15 million people worldwide receive a post-bite vaccination, which saves hundreds of thousands of lives per annum. Thanks to a comprehensive WHO Region of the Americas vaccination and response program that began in 1983, the incidence of rabies in humans and dogs has been reduced there by 95 and 98 percent, respectively. A similar program is underway in South-East Asia. Today, deaths from rabies aren’t that commonplace. Then, there’s Ebola. As noted by the WHO, Ebola first emerged in 1976 in two simultaneous outbreaks in what is now South Sudan and the DRC. The infectious malevolence has been in and out of the news over the last few years, and the latest outbreak had public health experts scrambling to work out whether or not it threatened those outside the Democratic Republic of the Congo (DRC). On average, those with the Ebola virus disease (EVD) have a 50 percent chance of dying – with a range of 25 to 90 percent in the past – but early care, featuring rehydration and symptomatic treatment cuts this somewhat. It has several zoological reservoirs, and is easily spread between people, which is why community education and engagement is key too. Although plenty of experimental vaccination programs are underway, none currently exist in the field, nor does the virus have a cure. Dr Nonia Pariente, the senior editor of microbiology at Nature, told IFLScience that the Marburg virus has a particularly high CFR. Although a laboratory-linked outbreak in 1967 had a CFR of 25 percent, an Angolan outbreak in 2004 registered an 88 percent CFR. Causing a viral hemorrhagic fever, it comes from the same Filoviridae viral family as Ebola. It’s similarly virulent, and can easily jump from human-to-human via physical contact and by handling dead infected animals, particularly monkeys and fruit bats. As with Ebola, no vaccine currently exists. It doesn’t affect many people around the world, though, and pretty much occurs near Rousettus aegypti, fruit bats that are natural reservoirs of the virus. You could also include HIV here, but this is a complex one. These days, an HIV diagnosis is often no longer synonymous with a death sentence. Phenomenal international health and biomedical research efforts means that times have changed since the outbreak began in earnest a few decades back: Those living with the infection not only can render themselves virtually unable to transmit the virus to others using medication, but they’re also able to live far more normal, longer lives. As explained by the WHO, massively expanded access to antiretroviral therapy (ART), better public education, and prevention methods have led to a “steep fall globally in the number of adults and children dying from HIV-related causes.” In 2015, about 1.1 million died from complications related to AIDS, 45 percent fewer than 2005, despite a period of substantial population growth in regions where the disease is prevalent. The UN has committed to ending the AIDS epidemic as a public health threat by 2030. Saying all that, there is no cure for HIV: its ability to assault our immune system makes it very difficult to deal with. The only person who has been cured is the so-called Berlin patient, whose riddance of the virus from his system remains a mystery. Mortality rates, therefore, vary wildly depending on the person’s health and their access to ART. Those with HIV/AIDS won’t necessarily die from it, but it does complicate things a lot. As noted by the University of California San Francisco, a person diagnosed with HIV at 25 who receives solid medical treatment is expected to live for 40 more years – but AIDS is a specter that waits in many of their futures. As is probably clear by now, a high CFR alone doesn’t make them more dangerous than other viral infections. Mortality rate is just one factor in the equation: How easy a virus can spread, the time it takes to replicate within an infected host, the type of community in which infection occurs, its ability to exist in various zoological reservoirs, our ability to immunize ourselves from it, and how quickly and effectively we as a species respond to an outbreak all play major roles. “Most viral diseases that we can avoid is down to the fact that we have effective vaccines to prevent them,” Pariente stressed. “Indeed, a very big killer was eradicated thanks to vaccines, smallpox, and we are on the verge for poliovirus.” Measles, of course, is another potentially deadly viral infection. Although almost eradicated in the last decade or so, Pariente laments that anti-vaxxer nonsense has resulted in delayed progress and yearly measles outbreaks now “notoriously in the US and Europe.” Deadly viruses can sometimes be treated with drugs too, but there aren’t many effective options available. “They replicate inside our cells using a lot of our machinery, and so to make a drug specific is hard," Pariente added. “If the drugs target the virus itself, they frequently become resistant – through mutation, recombination, re-assortment, depending on the virus.” At the end of the day, what’s deadliest now – whether that be in total number of deaths, CFR, or some other measure – doesn't always remain so, as the future may present us with entirely new challenges. Pariente pointed out that mosquito-borne viruses are proving to be particularly problematic. They are hard to control and continue to emerge and re-emerge in the tropics. Worryingly, “the mosquitoes that carry them are extending their niche due to global warming and getting into the US and Southern Europe.” Dengue, Yellow Fever, Zika, and West Nile virus can all be spread this way. Unsurprisingly, there’s a huge international health endeavor underway to better understand their epidemiology. Similarly, there’s also the worry that viruses may suddenly change to become far more deadly to humans than they were before. Influenza, of course, is a good example of that, and sadly this type of event is unavoidable. All we can do is make sure we’re as prepared as possible for the next pandemic – whatever it is, and whenever it arrives. A TRANSMISSION ELECTRON MICROGRAPH OF SEVERAL MARBURG VIRIONS. Source