Tags: Borrelia, Borrelia hermsii, Borrelia miyamotoi, health, Lyme Disease, medicine, New England Journal of Medicine, Relapsing Fever, tick bite, tick-borne relapsing fever
Several months ago, when the patient support group that I attend first began discussing Borrelia miyamotoi, a Google search (or Bing…whatever…) for those two odd words yeilded very little. Now, after the publishing of a few key papers in the New England Journal of Medicine, every major news outlet seems to be aware of this “new” Borrelia.
From a scientific perspective, Borrelia miyamotoi is interesting because it challenges a dichotomy that was established by researchers of tick-borne infectious diseases. When I first started reading about the Borrelia genus, I learned that Borrelia species could be sorted into two major categories: the Lyme disease-like group and the relapsing fever group. That is, Borrelia species like B. burgdorferi, B. afzelli, and B. garinii–which are genetically more similar, are carried by hard-bodied ticks, and cause the same pattern of symptoms (rash, joint pain, fatigue–were put in one group. Other species, like B. hermsii and B. parkeri–which differ genetically from these Lyme-like bacteria, are carried by soft-bodied ticks, and all cause relapsing fever symptoms–were put in the other group. One group for Lyme-like illness. Another group for relapsing fever-like illness. One group for hard-bodied ticks. Another group for soft-bodied ticks. The dichotomy is so clear that the ticks are sometimes referred to as “Lyme disease ticks” and “relapsing fever ticks.”
The funny thing about dichotomies is that they only create the illusion of two distinct categories. The reality is far more messy and characterized by shades of grey. Enter Borrelia miyamotoi. According to its genetics, it should go in the relapsing fever group, but it’s transmitted by the same hard-bodied ticks that carry Lyme disease. According to its symptoms, it falls somewhere in the middle. About 10% of people get a rash, like with Lyme disease, while others don’t. Some people get relapsing fevers, while others don’t. It’s all so very confusing!
As usual, both the researchers and the news media seem to be trying to downplay this. Some are unwittingly obscuring the issue altogether. “Paging Dr. House: There [sic] a new tick-transmitted spirochete in town…” writes Melissa Healey of the L.A. Times. “The New England Journal of Medicine on Thursday published two reports documenting its arrival on U.S. shores.” As if the bacteria hopped on a boat from Russia, and that’s how it got here! Forget the strong possibility that it was here all along and our scientists just failed to detect it. Forget the possibility that the countless numbers of people who tested negative for Lyme disease and were denied treatment could in fact have this similar infection.
Dr. Peter Krause, lead author on the NEJM study, says (in a video for Yale News) he doesn’t think people should panic about Borrelia miyamotoi. At the same time, he admits that this is an infection that is affecting people in both the eastern and western United States–not to mention people in Europe and Asia. “We expect this disease to be found everywhere the deer tick is found,” he states. So don’t panic, but it’s everywhere.
Okay, so Dr. Krause is right when he says people shouldn’t panic, but that doesn’t mean that we shouldn’t learn more about this new–or not so new, as the case may be–infection, especially since many of us could have it right now. Here are nine things I think you should know about Borrelia miyamotoi.
1. Symptoms: Borrelia miyamotoi causes symptoms of tick-borne relapsing fever (TBRF), an illness often misdiagnosed as Lyme disease, or not diagnosed at all. Tick-borne relapsing fever, when left untreated, has some symptom overlap with Lyme: arthralgias, myalgias, chronic fatigue, and cognitive problems; however, it differs from Lyme disease in that most patients with TBRF get repeated episodes of fever, and they don’t get erythema chronicum migrans (EM), the “classic Lyme” bull’s-eye rash. We can guess that the long-term effects of B. miyamotoi infection are similar to those of other Borrelia infections, even if researchers are reluctant to admit it. Dr. Peter Krause, one of the authors of the study published in the January 17 issue of the New England Journal of Medicine, told the L.A. Times: “This is a very new disease, but none of the patients have had this long-term [neurological] trouble or other long-term symptoms,[...] it’s possible that we just haven’t seen it yet.” Long-term neurological problems from a disease that most doctors didn’t know existed until a few months ago? I’d say it’s very possible.
2. Transmission: Borrelia miyamotoi is transmitted to humans from the bites of hard-bodied ticks. Examples of these ticks include Ixodes scapularis (deer tick), Ixodes pacificus (western blacklegged tick), Ixodes ricinus (castor bean tick), and Ixodes persulcatus (taiga tick). (The first two tick species listed are common in North America, and the second two are found in Europe and Asia.)
3. Why you’re just hearing about it now: The B. miyamotoi bacterium was discovered in ticks and mice in Japan back in 1995. (It’s named after Japanese entomologist Kenji Miyamoto, who first isolated the bacterium.) In 2001, Dr. Durland Fish discovered B. miyamotoi in ticks in Connecticut, but according to a 2011 New York Times report, he “was repeatedly refused a study grant [from NIH] until the Russians proved it caused illness.” In 2011, Russian scientists, in collaboration with the Yale team that included Krause and Fish, published research that showed that B. miyamotoi infects humans. The patients in the 2011 study were in Russia, so B. miyamotoi didn’t really come on the radar for U.S. doctors until January 2013, when a study on U.S. patients was published by Krause and colleagues in the New England Journal of Medicine.
4. Testing: To my knowledge, there is currently no commercially-available test for B. miyamotoi, be it PCR, IFA, or Western Blot. B. miyamotoi has been detected using assays (tests) that were developed by university researchers in order to study the bacterium. That means, unless your doctor is at Yale or another large institution, it’s not likely that he or she has access to a test for B. miyamotoi. So if you suspect you may be infected, what can you do? That brings me to my next point.
5. People with B. miyamotoi infection are likely to test negative for B. burgdorferi (Lyme disease), unless they also happen to be infected with B. burgdorferi. Doctors who are only screening patients for Lyme disease are not going to catch all of the other Borrelia infections, like B. miyamotoi.
6. Genetically, B. miyamotoi is more similar to other bacteria that cause TBRF, like Borrelia hermsii. Therefore, people with B. miyamotoi infection may test positive for B. hermsii, another relapsing fever spirochete.
7. As with any infection, B. miyamotoi infection can be more serious in the elderly and in patients with compromised immune systems. If you or a family member is denied treatment, especially in the case of severe or life-threatening symptoms (like high fever), my advice would be to go to a tertiary care center (like a university hospital) and ask to be tested for B. miyamotoi. At the very least, doctors at a research hospital should be able to do a blood smear to look for spirochetes (Borrelia). PCR and antibody tests may also be available.
8.Treatment: B. miyamotoi probably responds in a similar way to antibiotics as other Borrelia like B. hermsii and B. burgdorferi. Researchers claim that it can be treated with a few weeks of oral antibiotics, but that is probably only for mild, acute cases. My guess (as a non-medical-professional) is that B. miyamotoi is just as resilient as its Borrelia cousins and requires 4-6 weeks of daily IV antibiotics. If you’re new to this blog, you might be interested in reading about my experience being treated with IV antibiotics for B. hermsii (relapsing fever).
9. Recommended reading: To learn more about B. miyamotoi, check out the new fact sheet, which includes links to peer-reviewed studies.
Tags: antigens, Arthritis, Borrelia, Chronic Lyme disease, health, Infectious Diseases Society of America, joints, Journal of Clinical Investigation, Lyme, Lyme Disease, medicine, mouse, research, spirochete, steroids, Yale
As you may be aware, there is a great deal of controversy about persistence of Lyme disease symptoms after treatment—even when treatment involves long-term antibiotics. There are many theories about this, and several of them may be true, depending on the patient. The Centers for Disease Control (CDC) and the Infectious Diseases Society of America (IDSA) say that once you’ve been treated with a month of antibiotics, you no longer have a Borrelia burgdorferi infection. If you’re still experiencing symptoms, they call it Post-Lyme or antibiotic-refractory arthritis. At the other end of the spectrum, some Lyme-literate medical doctors (LLMDs) believe that Lyme is a chronic disease, and once you have it, you’ll have it for life. Long-term (read: indefinite) antibiotic treatment, they maintain, is necessary to keep the organisms from multiplying, but you’ll never fully be rid of them.
My views fall somewhere between these two extremes. (Disclaimer: I am not a medical professional.) On the one hand, I don’t think that four weeks of antibiotics, whether oral or intravenous, is really enough to kill off a Borrelia infection in a patient who’s been infected for years. (And this view is supported by Embers et al’s study of Rhesus macaques.) On the other hand, I don’t think that antibiotics-for-life is the answer either. There are just too many people who have been on antibiotics for years who don’t seem to be getting better. Plus there’s the fact that antibiotics can cause a lot of damage if you take them long-term, which significantly lowers the quality of life for people on these treatment regimens.
So when patients have been treated and they’re still experiencing symptoms, I see several possible explanations:
1) The antibiotics didn’t kill off all the bacteria, and they are still hanging around somewhere—perhaps hidden in joints, cartilage, or the brain. This, as you can imagine, is very difficult to prove, especially in living human beings.
2) The antibiotics killed off all the bacteria, but the patient was bitten by another tick and re-infected. This is highly possible if the patient’s environment, lifestyle, and preventive measures have not changed. It’s also difficult to detect when patients are only being follow-up tested with Western Blots, and not something like the C6 antibody assay, which gives you a titer so you can see if your antibodies to the bacteria suddenly increase. (A study related to reinfection was just published on Wednesday in the New England Journal of Medicine. You can read about it in the NY Times here, or read the study abstract. I’ll be doing a run-down of that study next week.)
3) The antibiotics killed off the bacteria, but the body is still making an immune response, possibly attacking its own cells, causing inflammation and continuing symptoms.
When new research comes out, I like to pay attention to see which of these explanations is supported and why. In this post, I’ll take you through a study called “Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy” that was conducted by some researchers at Yale and published in the Journal of Clinical Investigation back in June. (If you want to read along, you can access the full article here.)
The underlying question in this study is: what causes Lyme-associated arthritis in patients who have been treated with antibiotics? Is it that infectious spirochetes are still hiding somewhere in the body, or is it possible that antibiotics “kill” all the bacteria (read: disassemble them so they can’t multiply) but leave their building blocks (referred to as antigens because the body still detects them) behind, causing inflammation.
Let me explain how killing Borrelia in the human body works. The things you need to kill Borrelia are antibodies, first and foremost. If you don’t generate an IgM response, this infection can be fatal in the first 3 to 7 days. We know that IgM has a direct bactericidal effect. In other words, this antibody can kill Borrelia on its own in the absence of complement. IgG, by comparison, is very inefficient at killing Borrelia, but we make that, too. We also need phagocytes to kill Borrelia, and in order to generate antibodies, we need B cells that work. Another thing we need is toll-like receptors (TLRs). These are important for helping antibodies bind to pathogens or parts of pathogens. If we’re deficient in TLR2, or a certain molecule in TLR called myeloid differentiation antigen 88 (abbreviated MyD88), we can have an overwhelming infection.
What they did:
In this study, the researchers used a type of mouse in which this MyD88 protein has been knocked out—i.e. the mouse is totally deficient in MyD88. For that reason, they call it a Myd88-/- mouse. (No, that thing at the end is not an emoticon.) The problem with these mice is that they die quickly of opportunistic infection (specifically, Pneumocystis carinii), so in the lab, they have to give them an antibiotic called Sulfatrim or Septra, which is actually a combination of two antibiotics—sulfamethoxazole and trimethoprim. I’ll come back to why this is important a little later.
Now, an interesting thing is that this same group of researchers did a study back in 2002 using C3H mice, who don’t have the Myd88 protein knocked out—so essentially “normal” mice, in terms of their immune systems—and they showed that live Borrelia persist for 3 months after optimal treatment. These Borrelia that remained were sort of mutant Borrelia because they were missing a couple of proteins that they might need to infect other animals. The researchers knew this because the clean ticks that bit them got B. burgdorferi, but when they had those ticks bite healthy mice, those mice didn’t get infected.
Anyway, for some reason, these researchers didn’t want to use the C3H mice for this study, and they decided to use the Myd88-/- mice, who develop overwhelming infections. They also used a WT strain of mouse (which is not missing Myd88) for the sake of comparison. They infected both types of mice, and then they treated some of them with Doxycycline (through their water supply) and others with Ceftriaxone (via subcutaneous injection). Interestingly, they showed that after one day of Ceftriaxone therapy, they could kill all of the Borrelia. They also used an interesting microscopic technique which allows one to look real-time at tissue and watch an organism to see what it does. By cutting down to a mouse’s tendon, they can see what’s going on down there.
“B. burgdorferi DNA can be detected in B6 Myd88-/-, but not WT, mice after treatment with Doxycycline” (p. 2).
Translation: After treating the mice with Doxycycline, the researchers couldn’t find any B. burgdorferi DNA in the normal immune system mice, but they could find the DNA in the immune-compromised mice. One of those mice had a positive culture for B. burgdorferi, and ticks that fed on that mouse also tested positive for B. burgdorferi. HOWEVER, when they took samples from the knee joints of the mice, ALL of the mice tested positive for the ospA plasmid (B. burgdorferi DNA). In addition, ear-skin samples from half the immune-compromised mice and one of the normal mice tested positive for B. burgdorferi DNA (p. 2).
“Real-time imaging of B. burgdorferi in Myd88-/- mice reveals rapid spirochete elimination after antibiotic therapy” (p. 2).
Translation: The researchers used intravital 2-photon microscopy to observe the behavior of the B. burgdorferi spirochetes in the infected mice. Specifically, they looked at the dermis (skin) and the calcaneal (achilles) tendons. They say that 24 hours after beginning treatment with Ceftriaxone, the number of spirochetes had “diminished dramatically” in both the skin and tendons. The spirochetes left behind in the skin appeared to be moving, but the ones in the tendons did not. The following day, they were not able to see any spirochetes using this imaging technique, suggesting that they had all been destroyed.
“Spirochete antigens can be detected adjacent to ear cartilage in antibiotic treated Myd88-/- mice” (p. 3).
Translation: At the end of the study, the researchers took tissue samples from the ears of all the mice. They tested these samples for B. burgdorferi using both immunofluorescence staining (looking for antibodies) and culture techniques. The mice who were “sham treated” (not given antibiotics) tested positive. The mice who were treated with Ceftriaxone had negative cultures, but some “spirochete antigens” were detected in a deep layer of skin next to the ear cartilage. By “spirochete antigens,” they mean not live spirochetes but proteins (building blocks) left over from the bacteria that can cause the immune system to react. These antigens were found at a deeper level than where the imaging had earlier been peformed (which explains why they weren’t detected using imaging). The same antigens were detected in ear tissue from mice treated with Doxycycline. The researchers conclude that because the antigens were detected, but the bacteria could not be cultured (grown), it means whatever these spirochete remains were, they were incapable of multiplying because they had been too damaged by the antibiotics.
“Live imaging reveals antigen deposits but not motile spirochetes adjacent to cartilage of Myd88-/- mice after Doxycycline treatment for B. burgdorferi infection” (p. 3).
Translation: A separate experiment was conducted in which researchers studied mice between 2 and 10 weeks after finishing a 1 month course of Doxycycline. They used a technique called xenodiagnosis, where they let clean ticks bite the mice. They could find some B. burgdorferi DNA in the ticks that fed on the mice treated with Doxycycline, but when they studied the contents of the ticks’ guts, they could not find any spirochetes. By contrast, the ticks that fed on mice not treated with antibiotics had the bacteria in their bellies. In addition to using xenodiagnosis, they did the immunofluorescence test and cultures on this group of mice, and as before the cultures were negative and the immunofluorescence found antigens near the ear cartilage. This time, they used their imaging technique to look deeper under the skin, closer to the ear cartilage. In the sham treated mice, they found that there were motile (alive) spirochetes right next to the cartilage and large “deposits of nonmotile fluorescent material” where the skin meets the cartilage. In the antibiotic-treated mice, they saw no live spirochetes, but the same deposits were present next to the cartilage. So to see if these deposits would cause infection, the researchers transplanted skin from the infected mice (both those treated with Doxycycline and the sham-treated ones) into non-infected mice. Only the skin from sham-treated mice caused infection in the new mice. This shows that the antigens adjacent to ear cartilage in the mice treated with Doxycycline were not infectious.
“Spirochete antigens can be detected in joints of antibiotic-treated C3H Myd88-/- mice” (p. 4).
Translation: Here, the researchers decided to look at the knee joints of the mice to see if the same antigen deposits exist in antibiotic-treated mice. They looked at the knees of mice that had been infected for 4 months (which is a long time considering mice only live for about a year). When they treated these mice with Ceftriaxone, intravital microscopy showed that the spirochetes died off, but debris was left behind. They are pretty sure the spirochetes died off because the cultures were negative.
“Tissues from antibiotic-treated mice contain immunogenic and inflammatory B. burgdorferi antigens” (p. 4).
Translation: Finally, they wanted to test whether the deposits left behind in the knees of the mice actually contained B. burgdorferi antigens. They did this by immunizing new mice with knee tissue from the infected mice. They found that both the tissue from sham-treated and antibiotic-treated mice caused an IgG immune response to several B. burgdorferi proteins in the new mice.
Problems with the study:
1. It’s in mice. If you follow the research on B. burgdorferi, you’ll see that many of the studies are done in mice. That’s because it’s much less expensive to study disease in mice than in other animals. However, if we really want to learn about arthritis and B. burgdorferi in the human body, it would be better to do a study like this in Rhesus monkeys, which are much more similar to humans. Hopefully, this study will make it possible for some researchers to try to replicate this work in a primate model so that we can learn more.
2. The use of a “lab” strain of B. burgdorferi. They used a 297 strain of Borrelia burgdorferi which is “stable”–in other words, it’s not changing. It’s old and predictable. The problem is that most Borrelia in the wild are likely mutating and changing. They could even be developing resistance to antibiotics. After all, these organisms have been around for thousands of years; they are masters of adaptation. It would be much more interesting to do a study like this using a “wild” strain of B. burgdorferi, as this would more closely mimic the average patient’s experience.
3. The ambiguous blot analysis. The researchers used their own immunoblot to look at the antigens in the patellas (knees) of the mice. It’s not clear to me why they didn’t just use a Western Blot (since that’s the test used on us humans). Another odd thing they did was use a dilution of 1:1,000 for the blot, which is ten times the dilution used for other blots. Perhaps a lower dilution showed too many similarities between the sham group and the antibiotic group? In any case, for a study like this, I would expect more justification for these unusual choices.
4. The study’s “lack of heart” (and brain). I’m referring to the fact that the researchers failed to examine the effect of B. burgdorferi in the hearts of the mice. We know that, in addition to knee problems, patients with B. burgdorferi infections are at risk for a variety of heart problems, including myocarditis. The researchers were so bent on showing that antibiotics could kill the bacteria near joints, but what does that matter if the heart is still infected? If they truly believe that 24 hours of Ceftriaxone in mice eliminates B. burgdorferi, they missed a golden opportunity to show it by neglecting to examine the hearts–and the brains, for that matter. Not only did they ignore the heart, but they wasted valuable word space in their discussion section attacking the research design of Embers et al’s 2012 study of B. burgdorferi infection in Rhesus macaques. Now, the infamous monkey study is far from perfect, but they did do one thing right, which was to look at the heart tissue of the monkeys post-mortem–and guess what they found? In 3 out of 12 monkeys who were treated with antibiotics (that’s 25%), B. burgdorferi RNA could be detected in the heart. That’s despite the fact that in all 12 of the treated animals, C6 antibody titers decreased steadily over the course of treatment.
5. The use of septra/Sulfatrim. This one is a doozy. Earlier, I mentioned that the researchers added the antibiotic sulfamethoxazole-trimethoprim (Sulfatrim) to the mice’s drinking water “to reduce opportunistic infection”(p. 7). They claim that this drug has “no effect on B. burgdorferi infection or disease”(p. 7). I’m guessing they think that because of this 1996 study done in Austria. In that study, several species of Borrelia were evaluated to see whether they were susceptible to amoxicillin, azithromycin, cefotaxime, ceftriaxone, doxycycline, penicillin G sodium, roxithromycin, and trimethoprim-sulfamethoxazole (Sulfatrim) in vitro. The researchers used 30 different strains of Borrelia, but only 4 of those were Borrelia burgdorferi, and they were European B. burgdorferi at that. They found that B. burgdorferi was resistant to trimethoprim-sulfamethoxazole. Now, even though both ceftriaxone and trimethoprim-sulfamethoxazole were studied, the Austrian researchers didn’t investigate what would happen if you used both of these drugs on the Borrelia at the same time (which is what was done in the Yale study). In fact, after scouring PubMed, I was unable to find any synergistic Borrelia studies using ceftriaxone and trimethoprim-sulfamethoxazole. I did, however, find this study, also from Austria, published in 1997. They found that “trimethoprim was more active against Borrelia burgdorferi than against a sensitive strain of Escherichia coli, but sulfamethoxazole was not active against Borrelia burgdorferi.” In other words, one of the drugs that makes up Sulfatrim kills Borrelia, and the other doesn’t. The question is, if you add Ceftriaxone, does Sulfatrim start killing the Borrelia? To actually know whether or not Sulfatrim has an effect on B. burgdorferi when combined with Ceftriaxone, our Yale researchers would have had to do a synergy study, to see what would happen if you took the 50% kill rate of Doxycycline and Ceftriaxone, and add Sulfatrim. But they didn’t show that adding Sulfatrim didn’t affect the kill. So when they’re saying that “Ceftriaxone rapidly [within 24 hours] reduces pathogen burden in the skin,”(p. 5) they’re not taking into account that the Sulfatrim in the drinking water is also probably helping kill off spirochetes. It’s ironic how critical they are of other studies when their own study isn’t exactly “clean.”
6. The way Doxycycline was administered. Doxycycline was given to the mice in their drinking water. This means that the amount of Doxycycline in each mouse’s system depended on how much water it drank. The researchers said their reason for doing the Doxy in the water instead of force-feeding it to the mice twice a day was that when it was given twice daily, serum drug levels fell too low and they were not able to kill all the bacteria (p. 5). When I read this, I thought to myself, “Well, let’s see, how many humans do I know who are taking their Doxycycline through their drinking water? Oh, that’s right. None.” So here we have a study of Borrelia burgdorferi infection in mice in which the researchers choose not to give oral antibiotics because they believe not that the drug doesn’t work, but that the drug delivery system doesn’t work because it can’t get a high enough level of the drug into the blood stream. Yet, these are the same doctors who are saying that one month of oral Doxycycline should be enough to treat the same infection in humans. Curious, isn’t it? They even admit that one mouse may have stayed sick “due to a drinking pattern that led to inconsistent Doxycycline levels” (p. 5). So I guess either that mouse just wasn’t as thirsty as all the other mice, or he was eating his food and drinking his water in one sitting, and the food interfered with the drug absorption (as it can in people!).
7. They didn’t treat the arthritis. Okay, I get that the researchers were having lots of fun with their innovative real-time imaging technique. They tried to accomplish a lot with this study, and it already appears that they may have spread themselves a little thin. However, it bothers me that they spent no time examining ways to treat the arthritis caused by the deposits left behind by B. burgdorferi. In the world outside the laboratory, it doesn’t so much matter to people whether their arthritis is caused by live spirochetes or dead ones. They want to know what’s going to make them feel better. The study’s authors suggest that more antibiotics likely won’t work, but they don’t explore any alternatives, like steroids, for treating Lyme arthritis.
Some interesting (and some unexpected) implications:
1. Cool pictures. Intravital microscopy, the real-time imaging technology used in this study, is pretty nifty, and could be used in better-designed studies to find out a lot of useful information. The researchers in this study could even see some of the spirochetes changing into spherical forms, but they didn’t really investigate or discuss this in detail, beyond saying they don’t think those forms are bacterial cysts. It might be useful to have an entire study dedicated to investigating that.
2. Rethinking oral Doxycycline. It’s been my belief for a while now that oral antibiotics are just not as effective at killing Borrelia as IV antibiotics like Ceftriaxone. I’m not expecting everyone to agree with me on this, but let me tell you why I think so. While Doxycycline is by far the best choice among oral antibiotics for killing Borrelia (as it’s better at crossing the blood-brain barrier than many other drugs), there is an inherent disadvantage to all oral drugs because they have to be delivered through our digestive system. As a patient who took Doxy for a month, I can tell you that no matter how responsible and organized you are, it is very difficult to eat meals at the same time every day, to space the doses 12 hours apart, and to avoid ingesting things like milk that interfere with drug absorption. Reading Bockenstedt et al’s article made me further question the effectiveness of oral Doxy, as the researchers decided that oral Doxy twice per day would not be enough to keep serum drug levels consistent. Instead, they opted to deliver the drug through the mice’s water supply, which poses other problems with consistency. In any case, if it’s not good enough for lab mice, I don’t see how it’s good enough for humans.
3. A new drug combo? The study shows that in the presence of trimethoprim, you can rapidly kill Borrelia with Ceftriaxone. That means we should be doing more studies on how this works and whether it is safe for humans. There is always concern with killing off bacteria too rapidly because macrophages need time to clear the debris (which we think causes arthritis). However, this drug combination seems worth examining in other laboratory studies.
4. Location, location, location. The study doesn’t show that cartilage can be infected with Borrelia burgdorferi, but it does show that deposits are left over near cartilage after the bacteria have been disassembled by antibiotics. If the infection is in cartilage, that’s bad news, because there is no blood flow to cartilage, so it’s very difficult to eradicate an infection there. We need more studies that examine how this bacterium acts around cartilage.
5. Chronic Lyme? Contrary to what Yale alum and journalist Carole Bass would have you believe (Thanks to Becki from Bloody Lymey for opening my eyes to that one.), this study neither proves nor disproves the existence of Chronic Lyme disease, so despite the agenda that may underlie this study, patients need not see it as a threat. The study authors themselves admit in their Discussion section that they’re not quite sure what all their data mean: “The significance of B. burgdorferi DNA in xenodiagnostic ticks and in mouse tissues after antibiotic therapy is unclear” (p. 5). One possibility is that “Some B. burgdorferi DNA could remain intact if it is sequestered in cellular debris such as the GFP deposits.” They’re saying they think that the B. burgdorferi DNA they detected is just remnants of dead spirochetes that were preserved because they were stuck in the debris left behind by the antibiotics. However, they also admit to another possibility: “Alternatively, spirochete DNA could represent a minor subpopulation of B. burgdorferi that is not killed by the antibiotic treatment.” It’s a one-sentence admission in a 9-page paper, but it’s there–and it means that despite what these researchers think is going on, they still can’t say with 100% certainty that the antibiotics completely eradicated the infection.
What the study does show is that there are deposits in mouse tissue that the researchers insinuate are dead organisms (they have Borrelia antigens, are immunogenic, and don’t appear to be infectious). Because they don’t examine all of the tissue–including the cartilage, the heart, and the brain–it’s difficult to say whether they have completely eliminated the bacteria with antibiotics. What Embers et al showed in their primate model is that there seems to be persistence of spirochetes following 4 weeks of IV Ceftriaxone treatment and 8 weeks of Doxycycline. Until somebody does another study in Rhesus monkeys and proves that they’re wrong, that study stands.
6. Treating the arthritis. We know that reactive arthritis caused by Borrelia infections is a real phenomenon, and this study suggests that the cause is the debris left behind by spirochetes following antibiotic treatment. However, what patients and doctors alike need is access to information about how best to treat this unique form of arthritis. I’ve heard anecdotes from patients and doctors about the helpfulness of steroids like prednisone during or following antibiotic treatment, but there really isn’t enough research being done on this. It would be nice if researchers on both sides of the Chronic Lyme debate would pool their resources for the sake of better patient care.
I hope you enjoyed this installment of Tick-Lit Tuesday. It’s good to be back.
What has been your experience with Lyme or Tick-borne Relapsing Fever and reactive arthritis? What questions would you like to see addressed in future research?
What a difference a year makes! 07/14/2012Posted by thetickthatbitme in Patient Stories, Treatment.
Tags: Borrelia, Borrelia hermsii, brain fog, choline, energy, healing, health, IV antibiotics, Lyme Disease, medicine, pain, Relapsing Fever, ticks, treatment
A year ago yesterday was when I started my treatment for Borrelia hermsii. I left my home, my boyfriend, and my dog to stay with my parents so I could get treated with 42 days of IV antibiotics. Looking back on this time last year, so much has changed:
1. My knowledge level. I’m embarrassed to say that when I started treatment, I couldn’t even tell you if a tick has eight legs or six. (I never saw the ticks that bit me.) I knew nothing about the habitat or biology of ticks, and I didn’t know how many different diseases they can spread. I didn’t know how to spell Borrelia. Pretty much all I knew was that I was infected with a bacterium that was like Lyme but not Lyme that causes Relapsing Fever. This was strange to me because I never remembered having a fever–cold sweats, yes, but no measurable fever. I’d had IVs in my hand before when I’d been hospitalized, but I didn’t really understand what an infusion was, or that it mattered which vein a needle goes in. I had no idea what PubMed is. I’d read maybe three medical journal articles in my lifetime. Over those six weeks, I learned a lot from my doctor and other patients, and I kept learning through support group meetings and emails. Finally, I got up the energy and courage to launch this blog, and well…you know the rest.
2. My energy level. The fall of 2011 was when I should have realized something was wrong. I was student teaching in the mornings and teaching my regular classes at night. I remember what a struggle it was to get out of bed in the morning. Getting dressed was like running a marathon. I’d had back surgery the previous June, and I was in this hard brace that everyone called my turtle shell. But it wasn’t just my back that was a problem. Even with eight to ten hours sleep, by noon, I was struggling to stay awake. My 30 minute drive home on the freeway was terrifying. The only thing that kept my eyes open most days was if I was constantly chewing something, so I tried to always have snacks with me. When I got home, I’d take a 90 minute nap–which was never enough–and then I’d get up and go to work again. When the semester ended, I thought I would catch up on rest, but even only working part-time, I was constantly fatigued. I spent any time that I wasn’t working in bed. When I had to go on a business trip in March, I freaked out. How would I handle being on someone else’s schedule? How would I go six or seven hours without lying down? By June, I was freed from back braces, and my spine had healed, but I still felt awful. And I felt guilty. How had I become this lazy, unmotivated person who spends all her time in bed? A year later, I have my life back. I work two jobs, plus freelance work. I cook dinner for Boyfriend and me several nights a week, do all the grocery shopping, and keep the house clean. I walk my dog and ride my bike. I go shopping and to the movies with friends, drive long distances, and even occasionally babysit. Before, I only had the energy to do one or two of these things per day. I was a spoonie with a very low spoon limit. If I cleaned the house, that was it for the day. If I went to the store, I probably wouldn’t have the energy to cook the food I’d bought. If I taught a 3 hour class, I would come home and sleep the rest of the day. All of this I tried to conceal from my family and friends. I tried to be fine because there was no explanation for why I wasn’t.
Looking at how much better I am now makes me realize how sick I was. Yesterday, I had a two-hour morning conference call, after which I worked on the computer for another hour. Then I ate lunch and went to the grocery store. When I got back, I cleaned out the fridge, put the groceries away, and then did a thorough de-clutter and clean of the entire house. I read a chapter in my book, took a shower, and went out to dinner with Boyfriend. All that activity would never have fit into one day when I was sick. I was up again this morning at 8:00, feeling rested.
3. My pain level. I was on strong prescription painkillers for a year and a half, starting in June 2010 after my surgery. Clearly, I didn’t get off them when I was supposed to, 6-9 months post-surgery. That’s because I didn’t just have back pain. It was in my hips, neck, and shoulders, too. The pain didn’t completely go away right after treatment. It’s been a slow progression. In the fall, I was able to wean myself off painkillers and just use heating pads when my back or joints bothered me. We know from the research that reactive arthritis may simply be part of the package for some patients with treated Borrelia infections. This is my framework for understanding some of my continuing aches and pains. For me, low-impact exercise, comfortable shoes, heating pads, and a memory foam mattress pad help a great deal. Whereas before my daily pain level rarely dropped below a four, even with drugs, now I’m at a one or a two most days, and I’m drug-free, aside from very rarely taking Advil.
4. My cognitive level. The ability to think, speak, and write clearly is essential to my livelihood. Having a Borrelia infection plunged me into what many people describe as a “brain fog.” For more than a year, I was sort of drifting through life, not able to think very clearly about anything. It came on gradually, and after my surgery, it got worse, which I attributed to the pain and the painkillers. Now I’ve met enough fellow patients that I see the pattern. I understand how this infection clouded my cognition. One of the reasons I didn’t start writing this blog while I was getting treated was that I couldn’t focus well enough. Even post-treatment, it took me a few months to start feeling sharp again. I really noticed the change this past semester when teaching got easier. I was able to learn the names of all my students within the first three weeks–which hadn’t happened the previous four semesters. My focus and mental endurance were so much better, as was my time management during class. I felt sort of like I’d woken up from a long sleep. The time in my life when I was very sick seems blurry. Now, not only do I have the energy to do more, but I have much better concentration. I can even go back and look at things I wrote two years ago and see the difference in sentence structure. All I can say is it’s good to be “back.”
What I’m doing to stay well, one year out:
1. Eating my eggs. You wouldn’t believe how “off” I feel if I go a day without an egg. That’s probably because my neurologically-damaged body likes choline, and eggs are full of it. I also find myself craving green vegetables. In fact, whenever friends ask me where I want to eat, I usually say, “Anywhere with good veggies.” I know there are many diets out there that are designed to help people with Borrelia infections avoid inflammation and other problems, and many of those recommend avoiding meat, dairy, gluten, and sugar. Personally, I’m not really cut out for that. I’m not the kind of person who can say, “I’m not going to eat X” when X is something that I really like, like sourdough bread, or milk, or chocolate. That’s not to knock the vegetarian, dairy-free, gluten-free, and/or sugar-free diets. I recognize that they do work for some people. However, I’m pretty sure that my body needs both meat and sugar to function normally, so I’ve always been opposed to giving up those. Other than being lactose-intolerant, I have no problems with dairy, and I don’t have more pain when I drink my Lactaid milk than on days when I don’t, so I’m not so concerned with the inflammation factor there. I seem to tolerate gluten pretty well, but I do try to limit my grains, as they’re not the best source of choline. No one gets between me and my egg sandwiches, though.
2. Staying active. I spent a large percentage of a year in bed, and going back there is very tempting at times, especially since during that time I developed a large collection of movies and TV shows, and my bed is VERY comfortable. Because I used to do most things from bed, I’m just now getting used to LIVING in my living room, WORKING in the office, and SLEEPING in my bedroom. (In fact, I’m breaking this rule now, typing the first draft of this from bed, but it’s a Saturday, and I’ve been working all week, so I don’t feel bad.) For me, staying active means not only “working out” (by walking the dog, riding my bike, and playing Dance Central on Xbox) but “getting stuff done.” I used to put off doing things and tell myself, “I’ll do it when I’m not so tired, or when I’m in less pain.” Now I don’t have those excuses, and it’s much less burdensome to get things done right away. Procrastination used to be a form of self-preservation. Now it’s a habit I have to work to break.
3. Preventing re-infection. After what I’ve been through, the last thing I want is another tick-borne infection, so I make sure that both my dog and I stay out of high risk areas for ticks. When we walk, we stay on the sidewalk. Boyfriend and I keep the yard clean–which is not too difficult since our backyard is mostly concrete. We treat Lucy monthly for fleas and ticks, and I’m always spraying that Cedarcide. I’ve decided not to do any hiking or camping for a while. When I want to enjoy the outdoors, I ride my bike or go to the beach.
4. Staying current on my tests. I get my blood drawn every 3 months so my doctor can check my antibody titer. My doctor said if I have a four-fold rise, then we’ll need to consider re-treatment. So far, I’ve been okay, but I want to be vigilant. I don’t want to get re-infected and not know about it.
Hope everyone is having a wonderful weekend!
Six Tick Misconceptions 07/05/2012Posted by thetickthatbitme in Diagnosis, Prevention, TBI Facts.
Tags: Babesia, Borrelia, Colorado Tick Fever, health, Lyme Disease, medicine, misconception, Ornithodoros, prevention, Rickettsiosis, Rocky Mountain Spotted Fever, tick, Tick-borne disease
I have a confession to make. I have a phobia of most creepy-crawly things–roaches, mosquitoes, spiders, and especially ticks. When I see pictures of any of these critters, my first instinct is to shield my eyes. Ick! But what I should be doing is taking notice, so that if a tick ever gets on me again, maybe I can identify that little jerk.
Today’s post is about the misconceptions that many people have about ticks. As I warn frequently, there’s a lot of misinformation about ticks and the diseases they spread in the mainstream media and on the Internet. Here are six big misconceptions.
#1: Only deer ticks transmit diseases.
Deer ticks (a.k.a. blacklegged ticks) carry a lot of pathogens, including those that cause Lyme disease, Anaplasmosis, Babesiosis, and Bartonellosis, but they’re not the only ones you need to worry about. Dog ticks (Dermacentor variabilis) and wood ticks (Dermacentor andersoni) carry Rocky Mountain spotted fever (Rickettsiosis), Tularemia, and the Colorado Tick Fever virus. The lone star tick (Ambylomma americanum) carries Ehrlichiosis and the pathogen that causes STARI; bites from this tick have also been linked to a delayed allergic reaction to red meat. Two other types of Rickettsiosis, Rickettsia parkeri and 364D Rickettsiosis can be transmitted by the Gulf Coast tick (Amblyomma maculatum) and the Pacific Coast tick (Dermacentor occidentalis), respectively. Q fever (Coxiella burnetii) can be transmitted by the brown dog tick (Rhipicephalus sanguineus), Rocky Mountain wood tick (Dermacentor andersoni), and the lone star tick (Amblyomma americanum). Last but not least, soft-bodied ticks like Ornithodoros hermsi, Ornithodoros parkeri, and Ornithodoros turicata transmit Relapsing Fever-causing species of Borrelia. These ticks can live up to ten years!
#2: Lyme disease is the most dangerous thing I can get from a tick.
Though life-threatening complications like myocarditis can occur in the later stages of Lyme disease, B. burgdorferi infection is rarely fatal in the first months of infection. Many patients survive years without being properly diagnosed and treated. By contrast, Rickettsiosis (Rocky Mountain spotted fever) can be fatal in the first 8 days of symptoms (which vary greatly from person to person and don’t always involve the spotted rash) if it goes untreated. Female tick saliva also contains a neurotoxin that can cause tick paralysis, which can be fatal if the tick is not found and removed.
#3: I can’t get sick unless the tick is attached 36-48 hours.
While the CDC claims this is true for Lyme disease, if the tick has bitten you, there’s always a chance that bacteria or a virus is already in your system. Even if the tick doesn’t infect you with bacteria or a virus, you are still at risk for tick paralysis (see #2). In the case of soft-bodied Ornithodoros ticks, which spread Relapsing Fever Borrelia, feeding may only take a few minutes, and then the tick falls off, often undetected. (You can read more about soft-bodied ticks here.)
#4: If I don’t go hiking or camping, I’m not going to get bitten by a tick.
While participation in these activities does put you at higher risk for tick exposure, ticks can hide out in plenty of other places besides the forest floor, including the leaf litter in your yard. Ticks can hitch a ride into your yard on any of the wildlife on which they feed, including deer, mice, squirrels, and birds. They can hitch a ride into your house on your dog or cat. And don’t forget other four-legged friends like horses and sheep. If you have mice in your house or attic, you probably also have ticks. To avoid exposure, you should limit your contact with leaf litter, tall grasses, wood piles, and bird feeders. When hiking, stay in the middle of trails, wear long pants tucked into your socks, and wear repellent. Avoid sleeping in cabins that may be infested with rodents (and thereby ticks). After spending time outdoors or with animals, do a thorough tick-check. (This requires getting naked.) And if you’re a fan of spelunking, know that ticks—particularly soft-bodied ones—can live in caves too.
#5: If I don’t have a rash or a fever, the tick that bit me didn’t give me a disease.
At least 20% of people infected with Borrelia burgdorferi (Lyme) don’t have the characteristic erythema chronicum migrans (bull’s-eye) rash (EM). People with other tick-borne illnesses may be asymptomatic or have other symptoms (like joint and muscle pain or fatigue) that may not directly suggest an infection. That’s why it’s important to keep track of all of your symptoms following a tick bite, and to save the tick for identification and testing. You should always make sure your doctor is aware of any tick bites or tick exposures you may have had—and be clear about what regions/countries you’ve visited and what animal exposure you’ve had.
#6: I can use soap or Vaseline to remove a tick, and afterwards I should burn it with a match.
The proper way to remove a tick is with tweezers, grabbing the tick close to the skin, and using a slow, steady motion to pull it out. Using soap or Vaseline will not help you get a better grip on the tick, and may increase the likelihood that you squeeze the tick, causing it to regurgitate bacteria and other pathogens into your skin. Once you remove the tick, you should store it in a secure container and bring it to your doctor’s office for identification and testing. If you do get sick, it will be helpful to know what kind of tick it is and what pathogens it’s carrying. Don’t destroy the evidence with a match! If for some reason you can’t save the tick (because you’re too busy spelunking), at the very least try to take a picture of it. You’ll probably need a zoom lens.
So how do I spot them?
I usually try to link to pictures of ticks instead of posting them on this site because seeing tick photos can be a bit traumatizing to those of us who have been sick with tick-borne infections. However, for the purpose of prevention education, I’ve included pictures of all the ticks mentioned in this post (that I could find) in the slideshow below. You can read about the geographic distribution of hard-bodied ticks in the U.S. here and the habitats of soft-bodied ticks here.
- Four (surprising) places ticks hang out
- Infection Fact Sheets
- Major Misnomer: 8 things you need to know about Rocky Mountain spotted fever
Tags: antibody, Borrelia, Borrelia burgdorferi, Borrelia hermsii, diagnosis, IFA, IgG, IgM, laboratory testing, Lyme Disease, medicine, PCR, Relapsing Fever, Western blot
Two weeks ago, my infectious disease specialist, Dr. David C. Wright, who treated both of my tick-borne infections, was kind enough to grant me an interview during our Borrelia patient support group meeting, as well as a follow-up interview last week to clarify some points. The Q&A below is the result of those two interviews.
Em: Can you briefly explain 1) the way an immune response to a Borrelia infection works and 2) how well currently available tests detect this response.
Dr. Wright: The real problem we have detecting Borrelia infections is that humans don’t usually amount much of a response acutely to these infections. People can have millions of organisms in their blood and not have much of a response. Let me explain how this response works. One type of antibody we make is called IgM, which is for an acute response (to a new infection). Shortly after we make IgM, organisms clear from the blood stream. It’s been shown that IgM antibody can kill organisms in the absence of any other factor (you don’t need complement) and this may be the only infection where this occurs.
B cells make IgM antibody, and with time, switch to another class, IgG, of which there are 4 types, IgG 1, IgG 2, IgG 3, and IgG 4. The body eventually switches from making IgM to making IgG. Sometimes it happens, and sometimes it doesn’t. We don’t know why. Other people make an IgM response, then switch, and all we see is IgG.
For B. burgdorferi, we have a 2 tier system with ELISA and Western Blot. The ELISA is not very sensitive, and many doctors do not like to use it, relying more on the Western Blot. The way a Western Blot works is that proteins that are present in the organism are run on a gel, paper is put up against the gel, they run currents though it, proteins are transferred to the paper, and they are separated by weight. Kilodalton (kDa) is a measure of molecular weight, so a reactive 39 kDa band means the patient is making antibody to the protein that has a molecular weight of 39,000 daltons. For the IgM Western Blot, you need 2 of 3 bands positive for the test to be considered positive.
For the IgG Western Blot, the government (CDC) defines positive as 5 bands (out of 10 or 11). The sticky wicket of all of this is that the organism that is used is called a B31 isolate (from New York in 1982). Only one organism, one isolate, is used to detect antibodies. That would be all well and good if the world were a nice clean place and there was only one strain of B. burgdorferi and it never changed. Worldwide, there are probably about 14 or 15 isolates in the Lyme-like Borrelia group (and there are at least 10 different species in the Relapsing Fever group), so it’s silly to think that you could detect antibodies to all the Borrelia with an ELISA and a Western Blot, and that’s what the government and most doctors would have you believe.
Just to show you how stupid this is, I’ll tell you about an article published by some doctors in Scotland, “Local Borrelia burgdorferi sensu stricto and Borrelia afzelii strains in a single mixed antigen improves western blot sensitivity.” The authors said it doesn’t make any sense to use the B31 isolate of B. burgdorferi when they have different isolates in Europe. They have B. afzelii there, so they took that and added it to B31, and they picked up 14 more positive patients (who would have been told they didn’t have anything). The Scots are not radical; they’re smart. What’s important to ask is, what are the isolates in your neighborhood or state? We need to make Western Blots with those organisms.
We also need more tests available for the other Borrelia in the Relapsing Fever group. For example, we know there’s an unusual European-like isolate in northern California. Now there’s B. hermsii, B. miyamotoi, B. parkeri, and we don’t have Western Blots for those species. Fortunately, Borrelia do have common proteins. For example,there is a BDR gene sequence that codes for relatively conserved proteins across all Borrelia species. In many cases, there is up to 60% homology. Some people may make antibodies that cross-react with several different strains based on this common protein sequence. Another way to think about the Western Blot is, if we had other isolates (ideally 6 or 7), because of these cross-reactivities, we wouldn’t be able to tell people which organism they’re infected with, but we’d stop missing Borrelia infections, which is the real point of the discussion, and it’s not discussed, because they’re just focused on one organism. It’s like we have scientific blinders on.
Another problem is that many strains haven’t been grown, so we don’t have tests for them. For example, B. persica, which causes Relapsing Fever and is common is Israel, has never been isolated and grown.
Em: What should patients know about the interpretation of IFAs and Western Blots? If a patient’s B. burgdorferi Western Blot has only one or two reactive bands, does that mean he/she doesn’t have a tick-borne illness?
Dr. W: Interpretation is pretty much a mess, but we’re kind of stuck with the current definition of what a positive is, even though we have inadequate tests. The official opinion for the IgG Western Blot is that anything less than 5 bands is a negative Western Blot. That’s interesting, but arbitrary. This was all decided at a conference in 1994. To my knowledge, none of this was ever published in a peer-reviewed journal. It’s based on this conference and data that was presented there, which most doctors have never been able to review. Over time, blots change. Banding patterns change. Organisms mutate. The reading of these assays is supposed to be standardized, but some labs use a densitometry reading and others use just a visual inspection. So it appears not to be standardized.
An article published in 2010 by Dr. Gary Wormser and his colleagues at New York Medical College, Harvard, and the CDC admits that we could increase the sensitivity of the IgG Western Blot for B. burgdorferi by changing the definition of a positive from 5 bands to 3 bands. ”With a requirement of ⩾99% specificity, the greatest sensitivity was achieved using a cutoff of 3 of 11 specific IgG bands (18, 23, 28, 30, 39, 41, 45, 58, 66, and 93 kD plus VlsE).” Doing this allowed them to detect 33% more infections.
When I see someone with one, two, or three bands on a Western Blot, it makes me really nervous, especially if they have been partially treated. That’s when we have a problem, because we have interrupted the immune response that would occur if nothing had been done. So then really the patient is in limbo. Insurance companies won’t pay for treatment unless a patient has five or more bands. What we do here in clinic is if I think a patient has symptoms and signs of a Borrelia infection and he or she wants to be treated, we offer to treat them as a cash patient. If they want to try Doxycycline, we do that, but if they’ve been sick for many years, it probably won’t work, so we offer daily Ceftriaxone therapy for 4 to 6 weeks. Even after a patient finishes this treatment, I like to follow him or her for an extended period of time and order labs every three months.
Em: Why do some patients have only positive IgM and others have only positive IgG? Can you explain your theory about the difference between these two groups?
Dr. W: I don’t know for sure why this happens. Dr. Gary Wormser and his fellow researchers say that if you have a positive IgM response, it means nothing. Others have published a paper that says other bacterial infections are associated with persistent elevated IgM. IgM is made within the first 3-5 days of infection. In a serious infection like Borrelia hermsii, if you don’t make that response, you might die, because the doctors aren’t going to recognize the infection and aren’t going to treat you. That’s why people die of Borrelia hermsii. If patients make it through the first cycle of organisms, maybe doctors will pick up on it and they will survive because they are making IgM antibodies. Because we have sophisticated tests for B. burgdorferi, we find a lot of people who have persistent IgM and no IgG. We also find people with IgG and no IgM, and with antibody to the C6 peptide. I’m not sure all these people are infected with the same organism. I worry about a persistent IgM response; those people should be followed because that means you have a clone of lymphocytes that are making antibody consistently. This occasionally happens in lymphoma. The opinion of a lot of B. burgdorferi experts is that a persistent IgM response is normal. They see it, ignore it, and don’t order additional tests. I don’t agree with this approach, and I think these patients need to be followed (with periodic lab tests).
Em: Can you explain the concept of cross-reactivity and how it relates to the detection of tick-borne infections?
Dr. W: Borrelia have internal flagella that allow them to be motile. These are inside the membrane, and motility structures are preserved across species. In other words, Borrelia flagella have a lot in common. Motility is key to survival, so you can’t change it much evolutionarily. The proteins are similar, so you would expect if you’re going to have cross-reactivity, you would see antibodies to the 41 kDa flagellar antigen [on the Western Blot]. If I see that, it makes me wonder whether someone has another Borrelia infection, like B. hermsii, because they don’t have enough bands. In fact, that’s actually what you had, Em.* Other doctors say it’s a false positive caused by some other organism that has flagella, but that doesn’t make a lot of sense because it’s more likely that you’d have a cross-reactive antibody response with another Borrelia strain than with something like E. coli.
*I had a reactive 41 kDa band on my Western Blot, and my antibody test was positive for B. hermsii.
Em: What’s a C6 peptide assay?
Dr. W: C6 is a 26 amino acid peptide from the sixth invariable region of Borrelia burgdorferi. A positive C6 peptide assay means a person is making antibody to a protein (C6) found in just one Borrelia—B. burgdorferi. This assay was developed for use during the B. burgdorferi vaccine trial. The researchers knew cultures were frequently (false) negative, so this test helped distinguish between people who were infected and not infected. Doctors have forgotten about this. It’s a nice thing to follow because you get a titer (as opposed to reactive/nonreactive bands), and you can see whether that titer goes up or down as you treat and follow a patient.
Em: When should a PCR be used to detect Borrelia infections?
Dr. W: It’s very useful to test on serum, cerebrospinal fluid (CSF), and biopsies of skin lesions (like Erythema chronicum migrans). The problem is that even in the most capable hands, culture and PCR are only positive in 94% of people with Erythema chronicum migrans. (A paper published by Dr. Wormser and colleagues found that 6% of patients with Erythema chronicum migrans tested negative on five different PCR tests for B. burgdorferi.) It’s possible that the other 6% have another type of Borrelia infection. The problem in general with PCR is that most assays can’t detect less than 200 copies of an organism in a milliliter of blood, so a person can have an infection but a negative PCR. It is useful to do if you can get access to one. ARUP Labs has a PCR for B. burgdorferi that they can run on serum and cerebrospinal fluid (CSF). It’s useful to do a PCR if you think someone might have an acute infection and their blood smear is negative. Currently we don’t have a commercially-available PCR assay for B. hermsii in the U.S.
Em: What does it mean to “re-isolate the organism” following antibiotic treatment?
Dr. W: If we were to isolate an organism from a blood culture after treatment, it means the infection was either not adequately treated or the patient has been re-infected. We rarely isolate Borrelia organisms in a rural health setting because of delays with delivering samples to the appropriate laboratories.
Em: Are you familiar with the CD-57 + NK panel used by Dr. Stricker and others? Is it useful?
Dr. W: NK stands for natural killer cells. Dr. Stricker and other LLMDs have published papers saying that if you follow the CD57 level and it is low, it means a person has a B. burgdorferi infection. It’s an interesting concept; however, my guess is that the CD57 count might be low in other infections as well. I don’t usually order an isolated CD-57 test. If a patient is lymphopenic (has an abnormal lymphocyte count on his or her CBC), I will order a lymphocyte subset panel (CD4-helper cell, CD8-suppressor cell, B-cells, and NK cells). If I think the patient may be hypogammaglobulinemic, I’ll test their immunoglobulin levels to see if they can make adequate amounts of antibody. If the antibody levels are really low, it might interfere with our ability to detect a Borrelia infection or other infection using antibody-based assays (like Western Blot and IFA).
Em: What new tests are needed?
Dr. W: We don’t necessarily need new types of tests; we need additional tests for other organisms. There are approximately 30 species of Borrelia worldwide. We can’t grow them all, but the ones we can grow, we should have a Western Blot for. For B. hermsii, the BipA antigen, which was discovered in a federal laboratory, has not become commercially available, despite the fact that the antigen is specific for B. hermsii and antibodies generated to BipA would only be found in a B. hermsii infection. It also would be nice to have a PCR for every one of the Borrelia types. In addition, more time needs to be spent developing media to grow Borrelia that have not yet been cultured.
Many thanks to Dr. Wright for donating his time. If you’d like to learn more about his practice in Monterey, CA, you can visit his website: http://davidcwrightmd.com.
If you have questions for me or Dr. Wright about any of the information in this post, please leave them in the comments or drop me an e-mail.
Tags: Borrelia, choline, diet, Lyme, medicine, nutrition, pregnancy, tick-borne
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Choline (a nutrient found in beef liver, chicken liver, eggs, bacon and pork) status in pregnant moms has been found to affect cortisol levels in newborns. According to a study published by Jiang X, Yan et al., http://lib.bioinfo.pl/paper:22418088, these pregnant women were given either 930 or 480 mg/day of choline in their third trimester for 12 weeks.
Tags: Arizona, CDC, coinfection, dogs, doxycycline, fatality, Lyme Disease, medicine, rash, Rickettsia, Rocky Mountain Spotted Fever, tick, transfusion
The fact sheet for Rocky Mountain spotted fever (Rickettsia) is up today. Here’s the cliff notes version:
1. You don’t have to be in the Rocky Mountains to catch RMSF. There are four types of ticks in the U.S. that can transmit this bacteria to you: the American dog tick (Dermacentor variabilis), Rocky Mountain wood tick (Dermacentor andersoni), brown dog tick (Rhipicephalus sanguineus), and the Cayenne tick (Amblyomma cajennense). Cases of RMSF have been reported all over the U.S., and there have also been some in Canada. In 2008, all but 8 states reported cases of RMSF to the CDC.
2. Rocky Mountain spotted fever can be a deadly disease if not treated promptly. The national fatality rate is about 3%, but this rate is much higher in certain states like Arizona, where the fatality rate is 10%. This is likely due to delayed diagnosis.
3. Patients infected with the Rickettsia rickettsii bacteria that causes RMSF may experience any combination of the following symptoms: chills, confusion, fever, headache, muscle pain, rash, diarrhea, light sensitivity, hallucinations, loss of appetite, nausea, thirst, and vomiting. Though 90% of patients develop the spotted rash, this often comes late in the illness, so if other symptoms are present, you shouldn’t wait to get treated. Ten percent of patients never develop the rash.
4. RMSF can be diagnosed with a blood antibody test called an IFA (indirect immunofluorescence assay), but this test is often negative in the first week or so of infection. If you are showing symptoms of RMSF, your doctor shouldn’t wait for blood test results before putting you on antibiotics, because the longer treatment is delayed, the higher the risk of fatality.
5. RMSF is treated with Doxycycline in both adults and children. The usual course is between 7 and 14 days. The CDC recommends treating for at least 3 days after fever subsides.
6. Another way to get RMSF is by squashing ticks that you find on your dog (or anywhere else) with your bare fingers. When you squish a tick, the bacteria inside it can come out and enter your body through your skin. When checking your pets for ticks, always wear gloves, and use tweezers for tick removal.
7. Although very rare, it is possible to get RMSF from a blood transfusion. If you experience symptoms of RMSF following a transfusion, see your doctor right away.
8. The symptoms of RMSF can mimic those of other TBIDs, like Ehrlichiosis and Anaplasmosis. Luckily, all three of these are treated with Doxycycline.
If you want to read more about RMSF, check out the fact sheet, which is full of links to additional information.
A fellow patient shares her story 05/30/2012Posted by thetickthatbitme in Diagnosis, Patient Stories, Treatment.
Tags: Borrelia, Borrelia hermsii, Ceftriaxone, Ertapenem, health, IV, Lyme Disease, medicine, misdiagnosis, Support group, tick bite, treatment
When I started this blog, one of my goals was to somehow extend the community and knowledge base of my support group to other patients out there in the ether. Up to now, I’ve been doing this by sharing research, either that was introduced to me by my doctor or members of the group or that I stumbled upon on my own, and by sharing my personal journey. A few weeks ago, a third way of accomplishing this goal occurred to me: to let the voices of other patients from the support group speak through this blog. Today’s post is my first attempt at that. Leigh is a member of my Borrelia hermsii patient support group who has generously agreed to share her hermsii story. If you have questions for her, feel free to leave them in the comments.
I moved to a beautiful coastal area and once I discovered that I could watch grey whales migrating south from the shoreline, I would hike out, sometimes, twice a day to see them. I never saw the bug that bit me, but I had what I thought was a mosquito bite that developed a red ring around it about a week later.
A couple of days after the bite, I left for China where I spent much of the trip sick, which I attributed to the trip. I caught a cold with a fever, but then got somewhat better. Two days before we left for home, I had terrible stomach problems. The Chinese airports have fever detectors you have to walk through before you can board any plane. I loaded up on Advil, Tylenol and Pepto Bismol to get home. Still, all of my symptoms seemed explainable; travel, food poisoning, jet lag.
It was now week three and I at least knew that a rash around a bug bite wasn’t a good thing, but when I made an appointment with my dermatologist he wasn’t available for another three weeks. I didn’t know I needed to drop everything and run to any doctor, so I waited. I kept getting alternately sick and better. By the time I saw him I was having terrible headaches. I was also losing concentration and feeling a bit “foggy.” The dermatologist immediately thought it was Lyme disease because of the red ring, and prescribed a very low dose of antibiotic. On the way to pick up the antibiotic, I drove off the road, hit a tree and wrecked my car.
After a little research, I found a local Lyme specialist who prescribed three antibiotics, Zithromax, Ceftin and Flagyl, each twice a day. After two months of this, it wasn’t working. I had stomach problems. I was very weak, tired, I had terrible headaches and my neck hurt so bad I couldn’t hold my head up very long. I couldn’t drive. I would sit at my computer unable to use programs I had been proficient at. I would repeat myself in conversations. I would make phone calls at odd hours, unaware of the time. I couldn’t do simple math problems. I couldn’t bear loud noises or bright light. I lost my sense of balance. I was rarely up or awake. I thought I was dying. I was neglecting my son and my husband, who insisted I look for another doctor. I made appointments with four different doctors. Luckily, the first was a neurologist who insisted I make an appointment with a specific infectious disease specialist in our area.
My appointment wasn’t for a week, but I realized I wouldn’t make it through the next week and he saw me the next morning. He was so off the wall and quirky that I had a friend of mine, who is a doctor, make sure he was a legitimate doctor! He told me that if he could make me laugh, he could make me better. He retested me and though my initial tests had shown a slight positive for Lyme, this test showed a strong positive to Borrelia hermsii, which explained the weak cross reaction for Lyme, another Borrelia. All of the literature says Borrelia hermsii doesn’t exist at low altitudes, but I know what I know, and I was at sea level when I was bitten. I asked the doctor what made him even guess Borrelia hermsii? He said it wasn’t rocket science; Borrelia hermsii is more prevalent in the west, and Lyme in the east.
The doctor prescribed a treatment that I had read showed promise, intravenous Ceftriaxone for six weeks. At this time, I was introduced to another “Lyme” sufferer who tried to talk me out of seeing this doctor and wanted me to see her Lyme specialist. We decided to compare notes in six weeks to see who was doing better. At the end of my treatment, there was no comparison between us. I was much better and she soon became his patient. She also had Borrelia hermsii, not Lyme.
I continued to be tested; my results have not gone down to a negative reading and may not ever. It showed up again 6 months after the first treatment in the form of a four-fold rise in my titer, but at least I caught it before I had raging symptoms again. I was retreated with Ceftriaxone followed by Ertapenem.
It’s now been almost a year since the second treatment and I have my life back. I feel focused. I’m working and doing things with my family. I’m planning a trip to Alaska with them this summer. I think the neck damage will always be with me, but even it’s better and at least manageable. I am eternally grateful to the miraculous chain of events that led me to this doctor and this treatment.
I was fortunate that I discovered a doctor who believes in Lyme disease and other tick borne infections. There are many doctors out there, along with uncooperative insurance companies, who doubt that Lyme and Borrelia infections even exist. Because of this there are many Borrelia infections that we currently don’t have tests for. I have encountered some skepticism in the medical field especially as I seek treatment for the physical damage that was caused by the infection. I believe that when you know something is wrong you have to be your own advocate. Only time will tell if I’m over this. At least I’ve quit running into trees!
Tags: antibiotics, arthralgia, Bell's palsy, Borrelia, herx, Herxheimer reaction, Lyme Disease, medicine, myalgia, pulse, supplements, tachycardia
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This is part one in a multi-part series on vocabulary related to tick-borne infectious diseases (TBIDs). Today, we focus on symptoms. You can find all these terms and more on the Glossary page.
arthralgia: a fancy medical term for joint pain. The origin is Greek (arthro- = joint; -algos = pain). Arthralgias may be a symptom of injury, infection, illness, or an allergic reaction. They are a common symptom with TBIDs like Borrelia burgdorferi (Lyme Disease), Borrelia hermsii (TBRF), and Babesia.
myalgia: a fancy medical term for muscle aches. Myalgias can be a symptom of infection with Borrelia burgdorferi (Lyme Disease), Borrelia hermsii (TBRF), Babesia, Ehrlichia, Anaplasma phagocytophilum, Rocky Mountain Spotted Fever, Toxoplasmosis, Malaria, or Influenza. They can also be a symptom of inflammatory diseases like Multiple Sclerosis.
Bell’s palsy: This is a paralysis of the muscles in the face caused by damage to the seventh cranial nerve. It is often unilateral (only on one side), and it’s more commonly seen in patients with Borrelia burgdorferi. As you may know, one of the consequences of Borrelia infection is inflammation, and this inflammation can lead to loss of nerve function. You can read more about Bell’s palsy here. Patients with Borrelia infections may also have damage to the eighth cranial nerve (also known as the auditory vestibular nerve), which can result in tinnitus (ringing of the ears) and problems with balance.
postural tachycardia: Tachycardia is a heart rate that exceeds the normal range (usually indicated by a pulse greater than 100). Some people with infections have tachycardia all the time, but many only have postural tachycardia, which is tachycardia when you stand up for 3 minutes after lying down for 3 minutes. According to my doctor, this has been a great predictor of whether a patient has an infection, and he puts every new patient though the “tilt test”: lie down three minutes, have your vitals taken, stand up 3 minutes, have your vitals taken. Often, the difference in lying and standing pulse will decrease over the course of treatment.
herx: Herx is short for Herxheimer reaction (or Jarisch-Herxheimer reaction). It was named after dermatologists Adolf Jarisch and Karl Herxheimer in the late nineteenth century, who discovered it while treating Syphilis patients with mercury. (Fun fact: Herxheimer was a colleague of Paul Ehrlich, for whom Ehrlichia is named. They both helped found the University of Frankfurt. Not-so-fun fact: Herxheimer was murdered in 1942 by Nazis at Theresienstadt; he was 81.) A Herxheimer reaction can occur when one is being treated for an infection with antibiotics. It’s thought to be caused by the endotoxins that are released as bacteria start to die off. Herx are characterized by fever, chills, rigor (shaking), hypotension, headache, tachycardia, hyperventilation, vasodilation with flushing, myalgia (muscle pain), and exacerbation of skin lesions.
I’ve discovered a bit of an inconsistency when it comes to information available online and in published research about herx. Almost every Lyme patient blog I’ve ever read mentions herxing. I was herxing bad today, etc. Many patient and doctor organizations related to the treatment of Lyme Disease also discuss herxing. They characterize herxing as common among patients with Borrelia infections and as a sign that antibiotics are working. Herx seems to be used liberally as a term that means any sort of increased discomfort that a patient feels while undergoing antibiotic treatment.
For the sake of comparison, let me tell you how a medical textbook describes the Herxheimer reaction. I’m using as my reference Principles and Practices of Infectious Diseases, seventh edition (borrowed, not bought). I’ll start with the Herxheimer reaction as studied in patients with Borrelia hermsii (TBRF) infections. A herx in hermsii patients is characterized by severe rigors, increase in temperature, and decrease in blood pressure. The onset of reaction occurs within 2 hours of initial therapy and coincides with clearing of spirochetes from the blood. This means that in order to have the reaction you have to have spirochetes in the blood (which would be indicated by a positive blood smear). You’ll also notice that the reaction happens on the first day of treatment.
According to Principles and Practices, herx occur in 30-40% of patients with Borrelia hermsii infections. When a herx does occur, medical attention is necessary because there is a possibility of fatality. Aspirin is sometimes given to lower the fever. A saline infusion can be given to increase blood pressure. If the reaction is very severe, the patient may have to be given steroids. In sum, if you have an acute Borrelia hermsii infection and are treated with antibiotics, there is a chance that you will have a herx reaction the first day of treatment. If you are having a true herx, you will probably need immediate medical attention.
Now, you may remember that I had Borrelia hermsii, and upon reading the above information, I was really curious as to why I never experienced one of these reactions. When I asked my doctor about it, he explained that it was because I had a latent infection. In other words, I did not receive treatment until several years after I was infected. My body had already tried to fight off the bacteria, and had partially succeeded because my infection was no longer acute. This meant I did not have a high load of bacteria in my blood. So even though some days my joint and muscle pain worsened and I felt sick to my stomach, because I didn’t have the shaking, the fever, and the low blood pressure and because the bacteria was hiding in my joints, not in my blood, I never had a herx reaction. Dr. W went on to say that he has treated more than 50 people with B. hermsii infections, and he has never seen a herx in clinic. He has, however, seen some fever-chill reactions when patients with hermsii were being treated with Ceftriaxone. “And those weren’t herx?” I asked. He didn’t believe so; rather, he thought that the fever and chills were because Ceftriaxone wasn’t killing the bacteria quickly enough. When he switched those patients to Ertapenem, a stronger antibiotic, the fever and chills went away, and the patients saw improvement in their conditions.
Now here’s what Principles and Practices has to say about herx in patients with Borrelia burgdorferi (Lyme Disease). The reaction occurs during the first 24 hours of therapy, and consists of high fever, a redder rash, and greater pain. Some vasodilatation may also occur. The Herxheimer reaction occurred in approximately 15% of patients. Only 15 percent! That was shocking to read. There were also no reported deaths from Herxheimer reactions during antibiotic therapy for Lyme Disease.
Clearly, the rate of herx reactions in studies did not match my impression from anecdotal accounts from patients, so I asked Dr. W if he could offer any explanation. His hypothesis was that since most B. burgdorferi (Lyme) patients have latent (long-term) infections and not acute (new) infections, they are probably not having true herx reactions. However, since some doctors prescribe a lot of different supplements to be taken while patients are undergoing antibiotic therapy, perhaps some of the symptoms that patients feel are adverse reactions to the supplements. Because supplements are not subject to the same FDA regulation as pharmaceuticals, the companies that manufacture them are not required to prove their safety or effectiveness. Consequently, very little is known about how these products interact with prescription and over-the-counter medications. To read more about supplements and regulation, go here.
Here’s what I take away from all this:
- Herxheimer reaction is a medical term used to describe a specific set of symptoms in a specific set of patients (those with acute Borrelia infections) which may be life threatening (in the case of very high fever and very low blood pressure), particularly in patients with Borrelia hermsii infections.
- The term “herx” has been adopted by both the LLMD (Lyme-literate medical doctor) community and the Lyme patient community and has evolved into a generic, non-clinical term that means discomfort or worsening of symptoms that occurs multiple times throughout the course of antibiotic treatment.
- Just because a patient is experiencing discomfort does not mean he or she is having a true Herxheimer reaction.
- Contrary to what some doctors say, there is nothing worrisome about a patient who does not have a Herxheimer reaction, as they only occur in 30-40% of B. hermsii patients and 15% of B. burgdorferi patients.
- Some episodes of high fever and chills during antibiotic therapy might mean that the antibiotic is NOT working well enough. Patients sometimes benefit by being switched from Ceftriaxone to Ertapenem.
- Because some patients take a number of supplements in addition to antibiotic therapy and none of these are properly regulated by the FDA and studied in clinical trials, their effect on the body is unpredictable. It’s possible that some reactions that patients believe are Herxheimer reactions are actually reactions to other things they are taking.
- My Story (thetickthatbitme.com)
- Ceftriaxone (Rocephin): Is your doctor following directions? (thetickthatbitme.com)
- Curious about Tick-borne Infections? (thetickthatbitme.com)
Tags: Borrelia burgdorferi, Borrelia hermsii, Ceftriaxone, danger, DEHP, infusion, IV push, IV therapy, Lyme Disease, medicine, package insert, PICC line, PVC, Rocephin, syringe
Have you ever stored a frying pan with a plastic handle in your oven and then forgotten it was in there the next time you turned the oven on? If you have, you probably can’t use that frying pan anymore because the handle is melted off. That’s a situation that demonstrates why it’s important to use products the way the manufacturer intended.
Think about how many over-the-counter medications you might have in your medicine cabinet. They all have different purposes, right? Some are for pain, others are for allergies, and others are for cough and cold. You bought each medication for a specific purpose, and it won’t work for other purposes. For example, you wouldn’t take Zyrtec if your back hurts, just like you wouldn’t take Ibuprofen in the hopes that you’ll stop sneezing when you go outside.
You also have to follow the correct dosing and timing specified by the manufacturer. If your back ache is going to last for the next 10 hours, and the instructions say you can take two pills every 4 hours, you can’t just take 4 pills now in order to save time. If you’re a daredevil, you’re probably thinking to yourself, “Oh, that’s no big deal. I won’t die,” and you’re right, you probably won’t die from taking 4 Ibuprofen when you’re only supposed to take two. But if you failed to follow the manufacturer’s instructions every time you took Ibuprofen, and you took it every day for months, you would probably be doing some serious damage to your body.
Now let’s think about a prescription antibiotic called Ceftriaxone (or Rocephin). Ceftriaxone is used for IV therapy to treat a variety of infections, including Borrelia burgdorferi (Lyme Disease) and Borrelia hermsii (Tick-borne Relapsing Fever). The drug comes in a powder form, and it has to be dissolved (“reconstituted” is the official term) in a sterile solution before it goes into your IV. By the time most patients see the drug, it has already been reconstituted in solution inside an IV bag by a doctor or pharmacist. This means the patients have never seen the vial that the drug came in, and they certainly haven’t seen the package insert and read the instructions.
So why should you care what’s in the package insert? Isn’t that for your doctor to worry about? Wouldn’t a doctor who has treated hundreds of Borrelia infections know the right way to prepare and use Ceftriaxone?
See if you can answer those questions when you’re finished reading this post.
Storage and Stability Issues with Ceftriaxone
Shelf life. Depending on how it is stored, Ceftriaxone in solution may have anywhere from zero to ten days of shelf-life. There are two main variables that influence the length of shelf-life: what the solution is made of and what container it’s stored in. As you can see from the table below, Ceftriaxone can be reconstituted in a variety of sterile solutions. What’s in the solution determines how it should be stored and for how long. For example, Ceftriaxone in a solution of Dextrose and Sodium Chloride cannot be refrigerated, and it only keeps for 2 days.
Containers. Take a look at the above excerpt from the Rocephin/Ceftriaxone package insert. The only two types of containers it references are glass and PVC. Why? Because those are the only two types of containers in which Roche, the manufacturer, has studied the drug. They don’t know what happens to Ceftriaxone in solution if you store it in a container made of any other material.
So the next question is: Are doctors and pharmacists only storing reconstituted Ceftriaxone in PVC and glass?
My reaction: Whaaaa?
Okay, with the glass, I’m actually not surprised. I’ve seen a good number of YouTube videos featuring patients doing home infusions, and in none of them did I see any glass containers. But what about PVC? Oh wait, PVC! I know you! PVC is an acronym for polyvinyl chloride, a substance used to make all kinds of things from pipes to IV bags and tubes. The problem with PVC is that it contains phthalates, specifically one called Di-2-ethylhexyl phthalate (DEHP). Exposure to DEHP and other phthalates has been linked to all sorts of health problems, and it has been banned in the manufacture of toys in both the U.S. (2008) and the European Union (1999). More recently, Kaiser Permanente announced that it will no longer buy IV medical equipment made with PVC or DEHP, and other hospitals have followed suit. Maybe that’s because they read this study about how DEHP leached out of PVC bags containing lipid emulsions (a.k.a. liquid nutrition), or this study about how DEHP leeched into saline stored in PVC bags, or any of the other 50+ studies on TOXNET about PVC and infusions.
Taking these developments into consideration, if you’re doing home infusions with Ceftriaxone, your doctor or pharmacist probably isn’t storing the reconstituted Ceftriaxone in PVC containers—and if s/he is, s/he shouldn’t be! Moreover, since we don’t know anything about the shelf-life of Ceftriaxone in any other types of containers (besides glass), it’s probably not a good idea to store it in non-PVC containers either. What about storing it in IV bags or syringes? I asked Dr. W about this, and he said that these containers are not intended for storage. IV bags even say, “Single use container. When introducing additives, do not store.” Again, there is NO DATA on how well this drug stores in syringes and non-PVC IV bags.
“So what about glass,” you say. “Should I just ask my doctor to put the reconstituted Ceftriaxone in a glass container?” Well, glass is a better choice than PVC or some other container, and some solutions, like Dextrose, are still available in glass bottles, but if those bottles get even one little crack, you’re S.O.L. Another concern is that even when stored correctly for the amount of time allotted by the manufacturer, Ceftriaxone can lose up to 10% of its potency, which means that if you are using drug that was made up yesterday or a week ago, some of the drug that’s going into your system is inactive. I’ve heard reports of stored Ceftriaxone turning yellow after a few days in the fridge. Dr. W explained that this is a very bad sign, because a color change means a chemical change has occurred. (Think about what happens when the bread sitting on your counter turns blue.) I don’t know what the effects of inactive drug going into your system are, but I think ideally, you want the drug to be 100% active, which means you want the drug to be freshly prepared daily, if possible. I know this is a tall order for both patients and doctors, but I think that doctors who really care about treating their patients effectively should consider this approach. Not only does it make the most sense, but it’s also the way the manufacturer intended for the drug to be administered. Read below.
Notice how they say that in order to “minimize drug waste,” that is, to keep the drug from going bad, it should be “mixed at bedside just prior to administration.” This means they want your doctor to fix it up right before you get your infusion. Note the use of “rare” in the next sentence. It should be RARE that the drug is not infused right after it’s prepared. Instead, most doctors seem to be making up drug a week in advance and telling patients to pop it in the fridge with last night’s leftover spaghetti. No, don’t eat that hamburger meat that’s been in the fridge for a week, but if you want to infuse that week-old Ceftriaxone solution, go right on ahead.
Drug Delivery Issues with Ceftriaxone
Here’s where my YouTube favorites list really started to play like a horror movie. (Cue Hitchcock music.) I saw all sorts of scary things in addition to the violation of the don’t-store-in-anything-but-glass rule. I saw a little girl hold her PICC line tube in her mouth while she flushed it with saline. (Yeah, Mom, it’s great that she could do it all by herself, but do you really think that’s be best way to keep the line clean?) I saw a young woman in Australia reconstitute her own Ceftriaxone on her living room coffee table. Most disturbing, I saw patients giving themselves Ceftriaxone through PICC lines using a technique called “IV push.” Why did this scare me? Allow me to explain.
An IV push is when a syringe containing reconstituted drug is hooked up to the PICC line and pushed through in just a few minutes. It’s a method that seems, to me, to be favored by lazy nurses who don’t have 30 minutes to wait around while a home care patient gets a drip. Aside from being a lazy method, is it a dangerous method to use with Ceftriaxone? Of course. Why do you think it scares me so much! To see why it’s dangerous, you have to understand the manufacturer’s instructions for appropriate concentrations of the drug and for the timing of drug delivery.
Concentration concerns. According to the package insert, 40 mg/mL is the maximum concentration allowed for Ceftriaxone. If you are infusing 2 grams Ceftriaxone, you need to dissolve it in at least 50 mL of solution (2 g = 2000 mg; 2000/40 = 50). Last time I checked, 50 mL of solution doesn’t fit in a little syringe. If you use less than 50 mL of solution, you can’t be sure that all of the drug (which is in powder form) dissolves, and that’s bad because you don’t want powder going into your vein. Even if you do manage to dissolve all of the drug in less than 50 mL of solution, there’s no guarantee that it will stay dissolved in that high concentration. Remember, syringes aren’t made for storage, and the drug company hasn’t studied the shelf-life of Ceftriaxone stored in syringes.
Timing concerns. Ceftriaxone is meant to be infused, not injected into your vein. That means it’s supposed to drip slowly. In our fast-paced society, I know it’s tempting to want to speed things up. Some of my fellow patients in the infusion clinic were always trying to speed up their IVs behind the doctor’s back so they could get out of there faster, and when they were caught, they were strongly admonished for two reasons. First, the drug is most effective when infused slowly. Second, infusing a drug too quickly can cause dangerous adverse reactions.
So imagine you’re doing a three-minute IV push through a PICC line. That means you’re putting the drug into your system ten times faster than it’s supposed to go in. What will happen is that you’ll have a very high concentration of the drug in your blood stream, and then you’ll have quick fall-off. This can result in high toxicity if the drug precipitates to your gallbladder or kidneys. The result is that you might experience a gallbladder attack or even kidney failure. What’s worse is that since you are pushing the drug through a PICC line and not through a little vein in your hand, you’re putting the drug into a vein that goes directly to your heart. If it hits your heart too quickly, you could give yourself an arrhythmia or bradycardia.
The bottom line: Any doctor or nurse who wants to give you an IV push with Ceftriaxone clearly hasn’t read and understood the manufacturer’s instructions in the package insert and should not be considered competent to treat you with IV therapy.
So what have we learned today?
- Many doctors aren’t using Ceftriaxone (Rocephin) according to manufacturer instructions.
- Ceftriaxone has no proven shelf-life when stored in anything besides PVC and glass.
- PVC is dangerous and should not be used to store any drug you plan on putting in your body.
- Glass storage containers can crack and leak.
- Ceftriaxone MUST be dissolved in AT LEAST 50 mL of solution. Anything less is unstable and unsafe.
- Ceftriaxone in solution must NOT be stored in IV bags and syringes.
- Daily prepared Ceftriaxone is the only sure way to get stable and potent drug.
- Ceftriaxone must be infused over at least 30 minutes in order to be safe and effective.
- IV push is a dangerous method that poses serious risks to the patient, including complications affecting the gall bladder, kidneys, and heart.
Questions? Concerns? Crazy Ceftriaxone stories? I await your comments.