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Hank: Let's face it: nobody likes being sick! And for the most part our bodies protect us from all kinds of pathogens. Infectious disease causing things like viruses, bacteria, parasites, even fungi. Your skin and mucous membranes are physical barriers to keep out nasty microbes. Plus, some immune cells can scan for any foreign molecules and attack, that's your innate immune response. Then you have your adaptive immune response kicking into gear with other cells that make antibodies and specialized cells to target specific pathogens.

That way if a pathogen ever infects you again, your body should be ready to fight it off. But not always. Some pathogens are tricky. They can go dormant and tough conditions or even hide in your body without you knowing and reactivate to cause a latent infection. So because I'm sure you want to know about this, here are six of the sleeper agent pathogens that can come back to haunt you.

Let's start with varicella-zoster, the virus responsible for varicella zoster, also known as chickenpox. Today most kids are vaccinated for chickenpox, but if you were born before the mid-nineteen ninety's, you probably are familiar with this itchy red blister type rash, I know I am. It's a super contagious infection spread by skin contact or by inhaling droplets from someone else's sneeze or cough.

Our immune systems are tough so after a week or so the blisters will scab and fall off at the virus isn't necessarily gone. Anyone who's had chickenpox could have a latent infection called herpes zoster which you might know as shingles. Basically, the varicella-zoster virus becomes inactive and hides in your ganglia, clusters of nerves that are found all along your central nervous system. We don't really understand how, but basically the virus simplifies its replication cycle. Instead of making lots of new copies of itself, it only replicates a few important proteins.

As you get older, your immune system gets weaker, so the antibodies and specialized immune cells don't respond as well to pathogens. Varicella-zoster can take advantage of this and reactivated some people start multiplying and cause a latent secondary infection that's pretty different from chicken pox. Since the viruses were hiding in clusters of neurons, the shingles rash usually infects the skin along the nerves branching from the spinal cord, causing painful blisters stripes instead of pox marks. But there is a shingles vaccine if you weren't vaccinated for chicken pox as a kid, and it's treatable with antivirals and pain medications.

Another contagious rash-causing virus is the measles virus, which also causes a fever and flu-like coughing and sneezing. It's so infectious that around ninety percent of people near an infected person will become infected if they aren't immune, and the virus can survive in tiny airborne droplets for up to two hours.

Luckily the MMR vaccine is really good at preventing the spread of measles. But that doesn't mean that measles infection still don't happen in the US and around the world. And in rare cases, the measles virus can have a mutation that lets it cross the blood-brain barrier which normally keeps everything but essential nutrients from getting to the brain. Once the virus is in the brain tissue, the virus enters a latent period. Though we still don't know how exactly, it's likely that the mutations also help the virus stay undetected by antibodies.

It could be 7 to 10 years until a latent infection shows up with the virus-causing subacute sclerosing panencephalitis or SSPE. This disorder affects the central nervous system and can quickly get worse from mild cognitive dysfunction to motor difficulties and eventually coma and death. Even though it's rare, this severe disease is just one more reason why routine vaccinations are important. Otherwise the risks could be fatal.

But if you want to talk about real bad there's also human immunodeficiency virus or HIV, which specifically infects certain immune cells. You know, the ones, that are supposed to be fighting the disease. When this virus destroys someone's immune cells their immune system gets really weak and they can develop acquired immunodeficiency syndrome, which can make any infection very dangerous, even something like the common cold.

HIV doesn't necessarily cause AIDS right away or even ever in some people because it's really tricky. HIV can easily mutate some of its identifying protein markers for example, which lets escape the adaptive immune system. Plus HIV is a retrovirus, which is an RNA virus that makes DNA copies of itself that can be integrated into the DNA of host cells, in this case immune cells. When this happens, the incorporated viral DNA is called a provirus, and it only replicates a little bit, not enough to do too much harm.

During this latent stage, most HIV-positive people don't have any symptoms of illness depending on their age, genetics, and general health. And antiretroviral therapy can help keep the virus from progressing to more serious stages. But HIV can also hide in viral reservoirs: certain tissues like lymph nodes or the spleen that aren't affected by antiretroviral treatments witch can only kill the virus in the blood stream. Right now in tissue reservoirs, the virus can replicate at low levels without being wiped out. So if a person stops their antiretroviral treatment for example, HIV can come back out of those viral reservoirs with vengeance and the person usually will develop AIDS.

Some people have a genetic mutation in certain immune cell receptors that keeps HIV from infecting them, so researchers want to figure out how to translate that into a treatment. But other scientists are looking at ways to coax the virus out of these tissue reservoirs so that they can be killed through drug therapies.

So while HIV is extremely dangerous, transmission is preventable, AIDS is preventable, and HIV positive people can live long and relatively healthy lives.

Viruses aren't the only pathogens that can hide, though. Mycobacterium tuberculosis is a bacterial species that causes the disease tuberculosis or TB. It's pretty contagious; you can get infected if someone coughs or sneezes and you inhale those tiny bacteria filled droplets, and it is not a fun time. Those bacteria usually infect your lungs, and all that coughing leads to phlegm and eventually bleeding.

So different immune cells target the lung tissue and clustered together to form granulomas, which are like biological traps that keep the bacteria from spreading. The low oxygen environment inside the granulomas causes the bacteria to only activate a few necessary genes, stop replicating, and exist in a dormant state. In fact, it's estimated that a third of the population is infected with TB bacteria but most never have any symptoms or are ever contagious.

About ten percent of TB positive people have latent reactivation of the bacteria and we're not exactly sure why. It probably has to do with a careful balancing act between the pathogen and the host's immune system. Since the risk increases in immunocompromised people like HIV positive individuals, infants, or the elderly. TB is preventable through the BCG vaccine in children, but it may not be as effective in adults. There's a treatment too: a very strict regimen of drugs for several months. But because bacteria can develop drug resistance, new treatments are still being researched. Basically M. tuberculosis can turn the immune system's response against itself so the granulomas aren't a prison, but safe havens for survival.

Bacillus anthracis, on the other hand, is a really tough bacterium that makes its own safe haven. Although it usually spreads to humans from contaminated animals, this bacterium is most famous for being a potential bio weapon. A mysterious white powder could be infectious spores that cause the disease anthrax. Even though these bacteria don't hide in your own body like our previous examples to cause a latent infection, anthrax is worth mentioning because these spores are a latent form of certain bacteria. They protect the bacterial DNA in a hardened protein shell.

Spores can survive for long periods of time in lots of environments: extreme heat, extreme cold, certain chemical treatments, even some radiation. Anthrax spores, for example, have even infected new hosts after being frozen in icy animal corpses for nearly a century. Once inside the warm nutrient-rich environment of living host, the spores reactivate and grow into full-fledged bacteria that keep replicating.

Bacterial spores can infect a host through inhalation, ingestion, or any wounds in the skin. And depending on the route of the infection anthrax symptoms can include blisters and ulcers, fever, or swelling of tissues and organs. There is a preventable anthrax vaccine, but it's only give it to people who work in high-risk environments such as laboratory workers, animal handlers, or military personnel. It isn't the common infection, so there isn't a huge risk to the general population.

Anthrax is also treatable with antibiotics if they're given early enough and taken for months. And anything that dies from anthrax can become hosts for the hardy latent spores, making this bacterium a sleeper agent that's in it for the long haul.

Finally we have this strange parasite Toxoplasma gondii. It can infect most mammals and cause a disease called toxoplasmosis. But this parasite only sexually reproduces in cats. See, oocysts are resilient eggs that contain a dormant parasite called a sporozoite. These oocysts are microscopic and can survive in all kinds of environments where they can get eaten by intermediate hosts, such as rats or birds.

Inside any host, the dormant parasites are released from their eggs and become tachyzoites, which move into muscles and neural tissue through the bloodstream. There, the tachyzoites become bradyzoites, and form fluid-filled cysts. When cats eat infected rats or birds for example, the parasites can mate and reproduce in their intestines, making lots of oocysts that get pooped out to continue the cycle.

Humans are only an intermediate host, so the parasites won't sexually reproduce, and someone who is infected can still seem healthy during a latent period while the parasites hideout in cysts. But like many latent infections, when the immune system gets weaker with age or illness, the cysts can actively cause severe disease. Latent toxoplasmosis has been linked with severe neurological disorders including depression, schizophrenia, Alzheimer's, and Parkinson's disease, and if a mother becomes infected the parasite can affect unborn babies.

Unfortunately, there is no current treatment for toxoplasmosis, only prevention. Which doesn't mean that you should get rid of your cats, but just be careful around their poop and stay away from potentially contaminated food or water sources. So most of the time the best we can do is try to stay healthy and trust our immune systems to do their job and defend us against pathogens. Plenty of scientists and doctors are doing their best to find treatments that work for these and other extra tricky diseases.

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