One of the problems with Lyme is the spirochetes are able to find hiding places from both the immune system and antibiotics. This is common with other pathogens. If the Lyme spirochete is stopped with antibiotics before it widely disseminates, its not difficult to kill. Think about the Herpes 1 and 2 models. Once the Herpes virus gets inside your nervous system, its virtually impossible to kill since neither the immune system nor antivirals can get to it. The immune system and antivirals can stop an ongoing infection but then it returns later from its hiding place in the nervous system. The Lyme model is similar but with many hiding places and the more time the more disseminated. If you have not been treated in a while, the spirochetes come out of hiding and cause the immune system to cause inflammation causing a variety of symptoms depending on where the spirochetes go. When you take antibiotics, it typically kills all the accessible spirochetes. This results in an improvement in symptoms. But some hide waiting to return. So you stop the antibiotics and out they come. Until persistence is shown to be real, there will be no research searching for ways to address each hiding place. Persistence studies are badly needed. Different antibiotics are effective to varying degrees in extracellular places, the many intracellular places, pass through the Blood Brain Barrier kill Borrelia in forms without cell walls - the so called L-Forms, Cysts etc.. There has been some recent research that Borrelia may hide out in the Biofilms of other bacteria already in your body. If the spirochetes are able to hide inside Biofilms which are quite common in other pathogens, that's yet another hiding place. This is basically why so many antibiotic protocols are tried. One common sense based theory says that if you don't attack all the hiding places at once or in close proximity, you will never kill all the Borrelia. It may be possible that there are hiding places as in Herpes 1 and 2 that will never be cracked. This may be why its so hard to cure Lyme. It all depends on what hiding places are invaded. Getting to Lyme early minimizes dissemination to the many hiding places. Waiting till its highly disseminated is not good. That's why the lousy CDC 2T test the resistance to persistence studies is doing great harm. Write your congressman about forcing the NIH and CDC to revisit culturing - the gold standard and in human persistence studies using a culture. Until that happens, this nightmare will continue.