The possibility of persistence in Lyme disease is a complicated, but critical topic. As you know, there’s a lot of discussion in medical circles and on the internet.
Is a persistent infection the cause of your symptoms, or is it a post-Lyme inflammatory process?
The continued research makes me hopeful that we’re getting closer to some answers. Currently, there’s a lot of research that supports the possibility that Lyme can cause a persistent infection.
Dr. Embers’ Monkeys
Monica Embers at Tulane University published a paper in 2012 about the persistence of Borrelia burgdorferi in rhesus macaque monkeys following antibiotic treatment of disseminated infection.  Dr. Embers and her fellow researchers infected a group of these monkeys with Lyme disease, and after four months had gone by, treated them with doxycycline for 28 days.
After a month, host-dependent signs of infection like rashes, antibody response, and other symptoms varied based on the unique individual that was infected. The monkeys’ blood tests had gone from Lyme positive to negative, but when these animals were sacrificed for tissue studies and other advanced diagnostics, all of the monkeys still had viable Lyme spirochetes!
There was evidence of persistent, intact, viable, metabolically-active Borrelia burgdorferi. Twenty-eight days of treatment cured zero percent of the animals. The persistence of specific antibody production may not really reflect the actual infection of these animals, because when they do these tissue samples, they’re finding that the animals are still infected.
Four Months of Infection, Three Months of Treatment
In the same paper, these researchers reported on another study that started the same way, infecting monkeys with Lyme disease for 4 months. Then, they gave them a month of IV antibiotics (ceftriaxone) followed by two months of oral doxycycline. The same thing happened: the blood tests became negative. This time, when they sacrificed the animals, tissue studies showed that 27% of the monkeys were cured.
That means that 73% of the monkeys still had viable, infectious Lyme disease that could easily cause symptoms in them. If you look at the control group – the monkeys who didn’t receive the treatment – the blood tests of half of these animals went from positive to negative over the course of the study. Even without treatment, monkeys that had previously tested positive for antibodies became negative!
A Variety of Responses to Infection
Dr. Embers did other studies, as well, which found that the host monkeys showed their infection in different ways and had a variety of different antibody responses.  Some animals responded to certain proteins on Lyme disease but not others. Some responded to no proteins at all, meaning their blood antibody tests, like the typical Lyme antibody screen often run on humans, were negative.
Some tested positive only on skin biopsies, but not blood tests. Some were positive only when a sterile tick fed on them, so that the monkey infected the tick. There was a great variety in the diagnostics and how these each individual animal expressed infection. Few subjects developed the classic Lyme EM or bull’s eye rash.
Other animals that were negative seven months tested positive at 12 months. The results seem to be dependent on how and at what point the researchers did the testing, as well as what part of Lyme they’re looking for.
It was a diagnostic conundrum, but in the end, after the 1.2 years of the study, none of the animals were cured. This is problematic because even though this was a study with artificially-infected animals in a sterile environment with very few stressors, none of them were cured with the standard 28-day treatment.
In another paper published by Dr. Embers and associates, they reported that inflammation and intact spirochetes were found in a variety of tissue types, including brain, heart, skeletal muscles, urinary bladder and peripheral nerves. 
Why Does Lyme Persist?
Part of the answer is that bacteria, including those that cause Lyme disease, can cause persistent illness by hiding inside of cells. This intracellular localization makes it much harder for your body and all of our medical treatments to find them. When Lyme is hiding inside of cells you may be less likely to produce a good antibody response, making our standard lab tests less effective.
Another thing these organisms can do is go into antibiotic-privileged sites where antibiotics and antimicrobial herbs have a difficult time getting to them.
They also have persistent or dormant states like cyst, biofilm, and granule forms.
- Cyst forms occur when the spirochete rolls up into a ball, becoming metabolically inactive and protecting itself much like an armadillo. 
- Biofilms occur when the organisms group together and sequester fat, fibrin, and polysaccharides to protect themselves. These biofilms can be strong enough to prevent antibiotics from killing the organisms. 
Presence of Co-Infections
Both ticks and those who are bitten by ticks might be suffering from multiple infections, a phenomenon called co-infection. A deer tick carrying Lyme disease might also carry Anaplasma, Babesia, and Borrelia miyamotoi and maybe even Bartonella species. [6-10]. All of these diseases can be transmitted through a deer tick bite.
The problem is that when we develop tests for such diseases, we do so assuming there is only one infection at a time. We don’t have tests for Lyme and Babesia, only for Lyme or Babesia. No one’s really studied what happens if the infected organism has one or two or three different infections at the same time. One of the reasons our tests may not be so good is that there are too many infections going on for your immune system to respond properly.
Infections like this may persist because many of them go intracellular, suppress your immune system, or block detoxification pathways. Work out of Yale has suggested that Lyme and Babesia co-infection in the environment and in hosts like mice and ticks is much more common than previously expected. 
When people have more than one tick-borne infection at the same time, it can make symptoms more severe. It’s more difficult to diagnose because now you have symptoms that look like many different diseases rather than one. You kind of get a “combo platter,” so it’s not as crystal clear to doctors. This also makes treatment harder.
Research on Lyme Persistence
Some people insist that Lyme doesn’t persist because that’s what they’ve been told. While the research is not definitive at this point, there is mounting evidence that persistence is very probable, certainly in experimental animals.
I can’t say how much I appreciate these animals. We do studies on them because we can’t do it on people. I wish there was a better way to research without using animals, but we’re getting so much information that explains why so many people are suffering. It will help guide us to that next place and eventually eradicate these infections. That work is being done.
There’s also some work being done by Dr. Zhang at Johns Hopkins, looking at antibiotic combinations and figuring out how we can hopefully eradicate these infections in the near future. 
In the meantime, our best evidence shows that Lyme disease, in particular, has a high potential for persistence in the body, creating chronic infections.