Can anyone help me figure this out?

[EAMom]

Azithromycin also has anti-inflammatory properties which helps the CF. Here's a paper: http://www.ncbi.nlm.nih.gov/pubmed/16005266

[peglem]

Okay, I just read EAmom's response (we posted at nearly the same time). I'm wondering if carrier state may be because the active strep is contained in biofilms which hide them from the bodies immune system. I use the analogy of the biofilm as the "mothership" which is cloaked. (perhaps I've seen too much Star Trek). However, some mobile units are launched by the mothership (to find food, or possibly new sites to colonize). The body's immune system makes short work of these, but as soon as they destoy some, more are sent out. Meanwhile the critters that are safe inside the mothership are happily living and excreting toxins, and the immune system is none the wiser! This would explain why many children do not have symptoms(= immune response) with a strep infection-the immune response is not triggered if the immune system cannot detect the pathogen.

 

I wonder if this is what was happening with my daughter's chronic strep. ( I refuse to call it carrier state because that implies that it is benign, which it most certainly is not). About three days after each course of Ab, she'd test positive again & of course have the behavioral exacerbations that go with it.

 

So far, there is no approved test for biofilms, but researchers at Northern Arizona University have invented a way to test for the chemicals that the biofilm critters use to communicate. (or is it the stuff that the "cloaking device" is made from?) Anyway, the test hasn't made it to market yet.

[P_Mom]

EA Mom,

Just a question here.... I am just asking this because we have never used Zith, and I don't really want to switch if not necessary, but, all the posts about zith make me wonder about trying it...my son still has mild, residual symptoms,(fully recovered after first bout of PANDAS, this is second, and, perhaps the reason for the mild symptoms)......anyway, I know Zith carries a bit more risks as far as the liver is concerned, and it is very broad spectrum...also, it has been shown to fail with certain strains of strep. (it did not work for my husband when he got the same strep last summer that started it all) What I am wondering is this....you mentioned that it took 2 months for zith to clear your daughter...is it possible, at all, that the remission occurred because of the natural, slow, waning of the disease, or, are you 100% certain it was the Zith. Again, just asking because I would consider trying Zith if I had someone be able to tell me they were 100% certain it was the antibiotic that "cured" their kid.

 

what are your thoughts?

[Buster]

Hi PANDAS_denmark,

 

Your post was really interesting. I wanted to check whether your child was evaluated for Acute Rheumatic Fever (ARF) and what the differential was. I'd also be very interested in what is the dosage of your child's azithromycin and your child's weight.

 

As such I am very interested in finding a scientific paper (or more) proving (or to some extent proving), that PANDASkids DO have a reaction when exposed to streptococcus (and/or other bacterias/virusses).

 

Have you ever come across such a paper ???

 

Regarding proof, this is in essense the controversy between Kurlan/Kaplan and Swedo/Snider. The NIH has multiple studies that are showing a significant correlation between Streptococcal Pyogene and initial onset OCD/tics. http://intramural.nimh.nih.gov/pdn/recent_publications.htm

 

Probably the strongest of the papers showing correlation are Swedo's 1998 original work: http://intramural.nimh.nih.gov/pdn/pubs/pub-3.pdf and the literature review in 2003: http://intramural.nimh.nih.gov/pdn/pubs/pub-1.pdf.

 

Kurlan/Kaplan responded in their 2003 commentary that correlation doesn't imply causality and that the PANDAS diagnostic criteria was too broad and did not include sufficient differentiation to other diseases (namely Tourettes Syndrome which is Kurlan's specialty). Swedo replied to this in Pediatrics http://pediatrics.aappublications.org/cgi/reprint/113/4/907 that there was sufficient differentiation and that the suddenness of onset was a telltale sign. However, this was still correlation, not causality.

Please note that even with the huge amount of study (> 20 years) on acute rheumatic fever (ARF), ARF isn't shown to be

caused

by streptococcal infection just highly, highly correlated. This very high correlation is what causes propholaxis antibiotic but it isn't "proof". Proof is really hard since you have to show that the disease can't happen without the streptococcal infection.

In 2005, Kurlan/Kaplan then did a 2 year study that was published very recently in Pediatrics (June 2008) http://pediatrics.aappublications.org/cgi/...ract/121/6/1188 where they took kids with chronic tics (i.e., > 3 years of tics) and tried to see if there was any correlation with proven streptococcal pyogenes (i.e., positive throat culture and rising ASO titer). They found there was a correlation that was greater than chance, but that there seemed to be many other causes of exacerbations (i.e., that most exacerbations weren't only caused by streptococcal infection).

It's important to note that Kurlan was studying kids with severe tics whereas Swedo was studying kids with severe OCD begging the question whether tic-only kids should be included in a PANDAS subgroup. In addition, Kurlan and Kaplan were looking at kids with chronic conditions rather than sudden onset kids.

There were numerous problems with the conclusions from the study that I've posted here Problems with the Singer/Kurlan studies. However, the short summary is that causality is still not shown. To prove causality, you have to show that the result cannot occur without the "cause" (i.e., that the OCD or tics in these children couldn't come from some other cause). This is nearly impossible unless you are willing to infect children purposefully with strep -- Yikes! I can't imagine anyone funding that study.

 

So the best we get is the annecdotal data when kids come back into contact with strep. We don't have a study of exacerbation rates between kids on antibiotic propholaxis versus those not on antibiotic propholaxis.

 

What has been studied (Snider's work) is whether kids on one form of antibiotic have fewer exacerbations than on another form of antibiotics and this study showed that both azithromycin and penicillan were equally effective in prevention of strep reinfection.

 

Regards,

 

Buster

[Buster]

Carrier State and what is known ... warning -- this is a bit long

 

I debated about starting a whole new post about carrier state and might as this is starting to get somewhat far afield of the original post. However, peglam's comment about cloaked mother ships was a good launching point.

 

From the literature there seem to be four major phases:

• adhesion
  
• colonization
  
• invasion
  
• infection
  

Adhesion is about how the bacteria attaches itself to the skin or to a mucosal lining -- i.e., why isn't the strep wiped away. There was lots of study on this between 1970 and 2000 with the result that they think it is a combination of protein M, lipoteichoic acid and protein F.

 

Colonization has to do with growth. It is not at all clear what causes the limiting of colonization in carriers. Certainly some have shown that other bacteria/flora in the throat compete for various building block material so one bacteria can interfere with another bacteria's growth. On p.68 of Dr. Kaplan's book "Streptococcal Pharyngitis" http://books.google.com/books?id=YiYY86j9A...F0ih6D5yurBrejg Dr. Kaplan makes some very interesting observations that the streptococcal progenes cells seem to stop producing M protein in those with carriage. Kaplan observed that the mecahnisms that produced the "symbiotic relationship with the human host have not been identified."

 

Invasion has to do with penetration of the epithilial cells. There are two types of invasion: extra-cellular invasion and intra-cellular invasion. In extra-cellular invasion, the streptococcal pyogenes release a spreading factor (e.g., hyaluronidase) that destroys connective tissue and streptokinase (which indirectly destroys fibrin and prevents blood clotting). In addition, the strep produces stretolysin O which acts to kill phagocytes. The cloaking items (per peglam's comment) are things like the hyaluronic acid capsule that prevent easy detection by phagocytes (i.e, those cells that detect antigens). On intracellular strep, Kurlan notes in the above reference that strep that produces M1 proteins have the ability to penetrate cells. Again the exact mechanism isn't known.

 

So the theory about carriers was that they had "adhesion and colonization without invasion" -- meaning that if you did a throat culture you'd certainly get streptococcal pyogenes, but that for reasons not known, the strep hadn't penetrated/invaded. This state has been declared to be benign, but actually no one knows this. The strep is most certainly producing streptolysin O, streptolysin S, hyaluronidase, streptokinase, ... however, these seem either to not penetrate past the epithilial layer or to not overwhelm the immune system such that any "leak" is blocked.

 

Infection, on the other hand, is what happens when the invasion overwhelms the immune system's ability to keep up the wall of defense. During infection, the growth continues unchecked and antibiotics help by either stopping reproduction of the strep or by weakening the actual cell wall of the strep (penicillin). In addition many of the macrolides are immunomodulating and shift the production of Th1 versus Th2 cells. The Th2 get the stuff extracellular and Th1 gets the stuff that is intracellular (if it can find it). So essentially, antibiotics stem the flow, the immune system builds up a response and then overwhelms the bacteria (if it can find it all).

 

Breaks in skin, tooth extractions, dental work, ... all enable rapid invasion and infection since the protection of the epithilial cells is broken and the bacteria can get right into the blood stream and reproduce rapidly. In addition, the subsequent exposures to strep (or its exotoxins) seem to be much more severe and so the recommendation is for prophilaxis antibiotics for ARF and SC individuals.

 

So, why are carriers resistant to antibiotics?

 

Well, it isn't clear that they are. It seems that there is a class of carriers who are only colonized (i.e., have no other symptoms of strep -- no ASO titers, no Anti-DNAse rise, no sore throat, ...). For this class of carriers, its really, really hard for the antibiotic to reach the strep since it is really on the surface of the skin and not invasive. For the one who has some invasion (i.e., had some rise of ASO titers), it appears that the surface colonization is not killed by the antibiotic or the antibiotic can't get the intracellular versions until they burst. This is where the macrolides come in if this intracellular form is the cause of recolonization. This is certainly not proven but is hinted at in Kaplan's 2006 papers. Penicillin can take out the extracellular stuff so perhaps penicillin is enough if it stops the cycle of intracellular infection. Similarly, the macrolides holding the intracellular infection in check allows the immune system to take out the extracellular stuff. At this point, please know that this is all theories and as far as I know there are no papers on this topic.

 

Just to throw an entirely weird wrinkle on this, the recent Kurlan paper shows that ASO titers drop after long exposure to strep (even if the strep is untreated) -- indicating either the strep is changing in what it produces or that the body gets used to the Streptolycin O (sort of getting used to bee stings) and stops mounting such a defense. This sure raises questions about the effectiveness of ASO as a strep selection tool.

 

 

Regard,

 

Buster

[EAMom]

My husband and I are 99% sure it was the Azithromycin that sent dd into remission...we don't know if there is still some minute amounts of strep hiding out in her system which is 1 reason she is still on it.

 

We started Az. on June 2 (rx for 5 days). On days 3-5 we noticed dd was yelling at us less, mood slightly improved. Otherwise, there was not much change. After 5 days we debated whether to do more. We took her off for a few days (she went back to Amoxicillin prophalaxis). Her mood declined again (this was fairly subtle) after 3 days off the Azithromycin. Diana (also posts on this forum, our kids have the same psychiatrist) encouraged us to continue with the Azithromycin. We restarted the Azithromycin. About 3-5 days into the second course dd "decided she wanted to get better" and started eating 3 meals a day. Her contamination fears (which had been going on for 2+ mo.) also resolved at that point and her mood improved significantly. By 3 weeks into the Azithromycin, her restrictive eating was entirely gone (now eating snacks, cookies, completely normal 8-year-old stuff) and her OCD questions (eg "will this make me fat?", "will this make my stomach grow?", "does this have sugar in it?") were gone. At 1 mo. into the Az. she doing great but still had some (becoming less frequent) motor tics (not a big deal to us) and was still a little "edgey"...I'd say she was 97% normal. At 2 mo. into the Az. she was 100% (as far as we can tell.) No obvious tics, not edgey.

 

One thing that is interesting...Diana's son took about 10 days on Azithromycin to "really turn around" and this was the same with us, the most noticeable change was at the 10 day mark (when dd decided to "get better" and started eating 3 meals/day). Diana said her son's tics took longer to go away, just like my daughters. The other similarities were that (I think) both our kids had PANDAS for about the same length of time (several months) and it's even possible that both children were infected by the same strain of strep as we live only 20minutes from each other. Also, both kids were also about 7.5 years old when their PANDAS struck.

 

Re Diana and the Azithormycin... her son was doing well until they decreased the dose to 125mg/day and got exposed to strep again in July...he's better, back on 250mg/day, but not 100% which is why she's going to do the IVIG.

 

It makes sense to me that we wouldn't necessarily see a 100% overnight change on Azithromycin, esp. after 5 months of having an inflamed basal ganglia. I would imagine it takes a while for the brain inflammation go down and for anti-brain antibodies or strep toxins leave their systems.

 

Other things...we also were giving dd advil periodically since mid May. We think that helped, she often slept after the advil and often ate better after it. We started giving it consistently mid-june until early august (usually just in the morning). We think that helped with the neuroinflammation. We also switched from Lexapro to low dose of Prozac in mid May. The lexapro didn't help tics or ocd questions but did seem to help her eating and initially her mood. We took her off due to akathesia and possible seratonin syndrome. Originally our intention was to take her competely off of SSRI's when we stopped the lexapro but her anorexia nervosa came back in full force (2 pieces bread/24hours) as her seratonin levels decreased. So we put her on Prozac which she is tolerating well and appears to even be helping with her pre-existing social anxiety (shyness around adults including teachers/other kids' parents).

 

In April/May I had wanted to try omega 3's to help with inflammation/brain repair but the pills were too scary and big for dd. I did eventually buy some orange flavored fish oil but by that time she was already much improved and dh didn't want to mess around with another variable.

 

I'm also curious to see what will happen once dd gets exposed to strep this winter. Whether the Az. will carry her through or whether there will be an "allergic" reaction even if she doesn't get a true infection. We're still waiting and seeing...which is why I say dd's PANDAS is "in remission" and not "cured".

[EAMom]

I just wanted to add that not everyone does better on Azithromycin. For example Nurseq's son did better on Keflex, got worse when she switched to Azithromycin. Maybe it depends on the strain of strep or if the strep is intracellular?

[michele]

Did you have any trouble getting the azith prescription and "talking the Dr" into trying it. Without reports out there saying azith is the recommended treatment I have not found any Dr's willing to try it. Has anyone here ordered it from Canada and paid for it out of pocket? I am considering trying this. Maybe I should contact the immunologist to see if he would do a trial on azith instead of the omnicef. The omnicef does work at keeping the strep at bay but he does still gets behaviors that never go away like compulsions, poor motor skills verbal tics and the worse is the emotional issues. Thanks for the good info. I appreciate everyone sharing their experience with treatments that have helped.

 

Michele

I just wanted to add that not everyone does better on Azithromycin. For example Nurseq's son did better on Keflex, got worse when she switched to Azithromycin. Maybe it depends on the strain of strep or if the strep is intracellular?

[Buster]

On BioFilms ... here's a recent study...

 

Hi Peglem,

 

Here's a recent paper on biofilms that folks might find useful.

 

http://www.pubmedcentral.nih.gov/articlere...i?artid=1594624

 

"Therapeutic Failures of Antibiotics Used To Treat Macrolide-Susceptible Streptococcus pyogenes Infections May Be Due to Biofilm Formation"

 

 

Regards,

 

Keith

 

 

So far, there is no approved test for biofilms, but researchers at Northern Arizona University have invented a way to test for the chemicals that the biofilm critters use to communicate. (or is it the stuff that the "cloaking device" is made from?) Anyway, the test hasn't made it to market yet.

[peglem]

Thanks for the link, Buster. I do find biofilms so fascinating! It'll take me a while to digest all that though!

[EAMom]

Not really a problem to get the rx. One issue was that our ped. knew that Azithromycin cleared younger sister of her carrier state so it seemed reasonable that we should try it on her PANDAS sister. Also, we are persistent and I suspect she felt a little bad that she missed the initial diagnosis (sudden onset anorexia nervosa in a 7-year-old with tics, ocd, psychotic behavior...all in a previously normal kid...she should have figured it out IMO). Also, we told her about Diana's sucess with Azithromycin...and I believe at that point we were giving her Diana's information and told her to speak to Diana's son's pediatrician who is in the same big medical group (but different town) as our ped.

 

Our ped was leary about us using it long term...I think she is coming on board with that now. She actually has no choice now since the ped. neurologist and ped. rhuematologist agree that we should do the prophylaxis.

 

Dd's psychiatrist also was willing to write the Azithromycin rx for us (she did the refill after the 1st 5 days since our ped. was on vacation at that point)...

[Buster]

How kids react to strep while on antibiotics ...

 

Hi Diana,

 

There are two papers by Snider about symptoms while on prophylaxis antibiotics. The one in 1999 had all sorts of compliance problems. The followup study in 2005 ( http://intramural.nimh.nih.gov/pdn/pubs/pub-9.pdf ) showed equal effectiveness in suppression of PANDAS exacerbations by both azithromycin and penicillin. Strangely, that wasn't the original intent of the study, but was an interesting result.

 

I have dearly wanted to check with the authors about whether they've had any PANDAS kids who would have been classified as 'carriers' and whether these kids did better on zith or penicillin, but haven't done so.

 

There is no paper I believe showing how kids react to strep, etc. WHILE on antibiotics.

 

Regards,

 

Buster

[Indigo]

Now I am being tested for mono...it will take at least a week to get my results back. I'm so tired and my throat feels funny but not like full blown strep....however my dd is having a full blown PANDAS episode today. It's awful! We were given zoloft if we need it because we haven't been able to get her off the Tennex completely and we stopped it this week. But today is awful, the anxiety/OCD is awful, tantrums, crying all day, throat clearing tics. She's still on the antibiotics and on the diflucan. I'm not sure what to do for her today. Any thoughts for me? My DAN doctor is out of town this weekend but I guess I could call the doctor on call.

[CarolynN]

Hello,

 

I have to confess I have not read through all the links. So I don't know if anyone else mentioned what I am about to share. But I had to tell you what my family has done naturally to get rid of strep and it does work.

 

Here is a link in which I explained it to another forum member http://www.latitudes.org/forums/index.php?...art=#entry18107 .

 

In the above link I mentioned the grapefruit seed extract. Since then I have learned the best way to do it is get the liquid grapefruit seed extract. Put about 3 drops in about 4 ounces of water (it tastes horrible). Then you want to gargle with it. You do this about 3 times a day.

 

For my children I hid the grapefruit seed extract taste by putting 2 to 3 drops in lemonade or orange juice.

 

I learned a huge lesson though you do not want to over due the grapefruit seed extract (GSE). Last December I had strep and did this regimen to get rid of it but in the midst I gave myself a blocked saliva gland. I WAY over did the GSE not thinking about my mouth taking so much of something so bitter in. I must have been doing it 10 or so times a day. So again just don't overdue it. You could google grapefruit seed extract and strep. I am sure you will come up with all kinds of information. I know I did when I did it.

 

Anyhow it works especially if you catch it early on. You also want to really load up on the probiotics because you need the good bacteria to help fight the bad.

 

Also, just a side note, you might want to get into a naturopathic doctor because recurrent strep is a sign of some other underlying issue normally.

 

If it were me I would stay on a really good quality probiotic permanently if I was dealing with recurring strep.

 

Hope this helps some!

 

Carolyn