Archive for the ‘Treatment’ Category

Of Rabbits and Men

rabbit-meadow-1280x1024

Tularemia is known as a rabbit disease which is spread to those who handle them including hunters and cooks; however, at the recent Lyme Disease Association 17th Annual Conference on Lyme and Tick-Borne Diseases, Timothy Lepore, MD, FACS, surgeon at Nantucket Cottage Hospital, explained that it is also a disease of those who work with the land such as landscapers and farmers, as well as those who get bit by a tick. There are cases reported in every state but Hawaii, and many other wild and domestic animals can be infected. The highest rates of infection are in Arkansas.

Tularemia first appeared in the United States in Massachusetts in 1937 after importing 30,000 to 40,000 rabbits per year from Europe. Importing came to an end in 1947.

http://columbia-lyme.org/patients/tbd_tularemia.html
Francisella tularensis, a gram negative, aerobic, pleomorphic, highly persistent intracellular pathogen, spread via the lymphatic system can cause fever, chills, headache, myalgia, extreme fatigue, glandular (swollen glands), oropharyngeal (sore throat, nausea, vomiting and diarrhea, abdominal pain and intestinal ulcerations), conjunctivitis, pneumonic (dry cough, respiratory difficulty and chest pain), ulceroglandular (skin ulcer at infection site) and can be septic and lethal. Symptoms typically develop within three or four days of inoculation but can take up to 10 days.

Tests: Tests for Tularemia are not widely available but direct examination of biopsy specimens or secretions by fluorescent antibody or Gram or histochemical stains are often helpful. F. tularensis can also be demonstrated microscopically with fluorescent-labeled antibodies. Antibodies are not typically present in the first ten days after exposure. Patient samples should come from sputum or pharyngeal washings, as the organism is not present in large numbers in blood. Polymerase chain reaction (PCR) tests can also be utilized. It is imperative that lab personnel take strong precautions as it is quite easy to become infected.

Treatment: Antibiotic therapy with Gentamicin (5mg/kg/day, IM or IV) or streptomycin (1 gm twice daily, IM). The recommended treatment period is 10 days. In vitro susceptibility studies indicate that quinolones and fluoroquinolones are also effective against F. tularensis, thus providing an additional option for physicians. Tetracyclines and chloramphenicol can also be used, but a higher rate of relapse is associated with these agents, as they are bacteriostatic rather than bactericidal. Thus, it is recommended that treatment with these medications be extended to 2-3 weeks. If treatment is initiated quickly the mortality rate for tularemia is around 1-2%; however, one-third of untreated patients will die, usually from pneumonia, meningitis or peritonitis.

http://www.idph.state.il.us/public/hb/hbtulare.htm
Transmission: Transmission can occur through the skin or mucous membranes when handling infected animals as well as through tick bite, contact with fluids from infected deer flies, mosquitoes or ticks, handling or eating undercooked rabbit, drinking contaminated water, inhaling dust from contaminated soil, and handling contaminated pelts or paws of animals. It can also be inhaled from infected hay, grain, or soil. Dr. Lepore had patients who contracted it from their pet dog who shook rain water on them after chewing on a dead rabbit, as well as from folks eating road kill, a person who held sick animals, and a gentleman who slept with his pet bunny.
http://www.siumed.edu/medicine/id/tularemia.htm
Tularemia, in aerosol form, is considered a possible bioterrorist agent that if inhaled would cause severe respiratory illness. It was studied in Japan through 1945, the USA through the 60’s, and Russia is believed to have strains resistant to antibiotics and vaccines. An aerosol release in a high population would result in febrile illness in 3-5 days followed by pleuropneumonitis and systemic infection with illness persisting for weeks with relapses. The WHO estimates that an aerosol dispersal of 50 kg of F. tularensis over an area with 5 million people would result in 25,000 incapacitating casualties including 19,000 deaths.

In a mass casualty situation – treat with oral agents for 14 days using Doxycycline (adults 100mg by mouth twice a day, children under 45kg 2.2 mg/kg by mouth twice daily) or Ciprofloxacin (adults 500mg, by mouth twice a day, children 15mg/kg by mouth twice a day).

Those performing autopsies should avoid bone sawing or any procedure likely to cause aerosolization and exposed people should wash with soap and water. In environmental contaminations use a 10% bleach solution for spraying and cleaning using alcohol 10 minutes after using bleach. There have been no reports of human to human transmission.

Category:

Ticks, Treatment, Tularemia

Study on Ceftriaxone

http://journal.frontiersin.org/article/10.3389/fmicb.2016.01744/abstract

Abstract

Although the majority of Lyme disease patients can be cured, at least 10-20% of the patients continue to suffer from persisting symptoms such as fatigue, muscular and joint pain, and neurologic impairment after standard 2-4 week antibiotic treatment. While the causes for this post-treatment Lyme disease symptoms are unclear, one possibility is due to B. burgdorferi persisters that are not effectively killed by current antibiotics such as doxycycline or amoxicillin used to treat Lyme disease. A previous study showed that four rounds of ceftriaxone pulse dosing treatment eradicated B. burgdorferi persisters in vitro using a relatively young late log phase culture (5 day old).

In this study, we investigated if ceftriaxone pulse dosing could also eradicate B. burgdorferi persisters in older stationary phase cultures (10 day old) enriched with more resistant microcolony form of persisters. We found that ceftriaxone pulse dosing could only eradicate planktonic log phase B. burgdorferi spirochetal forms and round body forms but not more resistant aggregated biofilm-like microcolony persisters enriched in stationary phase cultures. Moreover, we found that not all drugs are suitable for pulse dosing, with bactericidal drugs ceftriaxone and cefuroxime being more appropriate for pulse dosing than bacteriostatic drug doxycycline and persister drug daptomycin.

We also showed that drug combination pulse dosing treatment was more effective than single drug pulse dosing. Importantly, we demonstrate that pulse dosing treatment impaired the activity of the persister drug daptomycin and its drug combination against B. burgdorferi persisters and that the most effective way to kill the more resistant biofilm-like microcolonies is the daptomycin/doxycycline/ceftriaxone triple drug combination without pulse dosing. Our findings indicate pulse dosing may not always work as a general principle but rather depends on the specific drugs used, with cidal drugs being more appropriate for pulse dosing than static or persister drugs, and that drug combination approach with persister drugs is more effective at killing the more resistant microcolony form of persisters than pulse dosing.

These observations may have implications for more effective treatment of Lyme disease. Future studies are required to validate these findings in animal models of B. burgdorferi persistence.

http://journal.frontiersin.org/article/10.3389/fmicb.2016.01744/abstract

Free, full provisional text (pdf file, 2.31 MB):
http://journal.frontiersin.org/article/10.3389/fmicb.2016.01744/pdf

Category:

Lyme, research, Treatment

Mycobacterium Drugs For LD

Back in May you may remember the article about Dr. Horowitz having success with Dapsone, a drug commonly used for Leprosy, in his MSIDS patients that didn’t respond well to conventional treatment.  https://madisonarealymesupportgroup.com/2016/05/09/leprosy-drug-for-lyme/.  It was reported that patients improved in all symptoms except for headache.

Recently he and Phyllis R. Freeman published on another mycobacterium drug, pyrazinamide, (PZA).  https://www.jscimedcentral.com/Arthritis/arthritis-1-1008.pdf

He states in the study that co-infection is the rule and that one recent study showed 45% of ticks were co-infected with up to five different pathogens, with up to eight identified in the same tick.  Patients who have Lyme (borrelia) and are co-infected are much sicker and often resistant to standard therapies and often have varied clinical presentations making them harder to diagnose and treat.

The case study has based on a woman with Borrelia burgdorferi, Borrelia hermsii, possible prior exposure to tularemia, exposure to Mycoplasma pneumonia, multiple viruses, fibromyalgia, and rheumatoid arthritis.

This poor woman had been through hell and back for years.  Under Dr. Horowitz’s care she improved from 30% to 50%, but with the addition of Dapsone had a sudden fourfold increase in tularemia titers as well as Bartonella titers turning positive.

While making continuous progress the patient had ongoing joint pain which interfered with sleep as well as ongoing severe blood-filled blisters, oral/genital ulcerations, and increased granulomas.

While a rheumatologist wanted to put her on an immunosuppressive, she and Dr. Horowitz chose to try 500mg (based on body weight) of PZA twice a day combined with rifampin and minocycline.  Her liver was monitored every two weeks and was helped with alpha lipoid acid 600mg and milk thistle 250mg.

Two months later she reported up to 80% of normal functioning, had improvement in her most resistant dermatological symptoms with the resolution of her oral ulcers, and stated that it was the best protocol she had done in the past 20 years.

Horowitz reports that the Dapsone and PZA protocols have been the most effective treatment additions for resistant Lyme and autoimmune symptoms, with PZA being the most effective for dermatological manifestations of Bahcet’s and arthritic/granulomatous changes.

 

 

 

 

Category:

Lyme, research, Treatment

How Spirochetes Evade

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http://journal.frontiersin.org/article/10.3389/fimmu.2016.00385/full#h1

The various strains of borrelia that cause infection are tenacious, pleomorphic (shape-shifting) pathogens which are a bit of a cross between bacteria and fungus.  Anyone infected by them understands the war they wage in the human body and mind.

This excellent review shows the ability of spirochetes to evade the innate immune system.  One way they do this is by binding with human compliment regulators to prevent complement-mediated killing.

The author states that up to five distinct outer surface lipoproteins (CRASP) have been identified but that there have been various names given historically that cause confusion.  Please see table in the link above to understand this better.

The take home:  borrelia is tough to kill and effectively evades the human immune system.  It can morph between spirochete, cell wall, and non cell wall forms, necessitating combination antibiotic treatment that targets every form.

For more information on treatment, read:  https://madisonarealymesupportgroup.com/2016/02/13/lyme-disease-treatment/ and https://madisonarealymesupportgroup.com/2016/08/09/dr-paul-duray-research-fellowship-foundation-some-great-research-being-done-on-lyme-disease/  (The last link outlines microbiologist Tom Grier’s work showing spirochetes hiding in parasitic worms inside the human body, necessitating anthelmintics to effectively kill them).

 

Category:

Lyme, Treatment

C-diff and Anthelmintics

http://patient.info/health/clostridium-difficile-leaflet
MSIDS (multi systemic infectious disease syndrome – or Lyme with friends) patients visibly wince at the mention of C-diff (Clostridium difficile), a bacteria found in the gut that can force you to quit your treatment. For some, it can cause life-threatening inflammation of the bowel.

The challenge with C-diff is the spores which can be quite resistant. These spores can stay on surfaces for years and spread in the air when disturbed – such as when someone changes the sheets that an infected person has slept in. They can also get into food and other objects particularly if the infected and/or carriers of the spores don’t wash their hands properly.

To healthy folks this posses little to no risk of infection, but if your immune system is weakened due to an infection such as MSIDS, and then you are taking antibiotics to fight the infection, you are more likely to get C-diff than a healthy population due to the changes in the gut which upset the balance of healthy vs unhealthy bacteria.

While the majority of cases occur in health care settings such as hospitals, MSIDS patients are at risk because the antibiotics that are found to lead to C-diff infections are broad-spectrum antibiotics most commonly used in MSIDS treatment such as fluoroquinolones, cephalosporins, penicillins, and clindamycin. Also, using multiple antibiotics over a long period of time, (which is precisely a common treatment for chronic MSIDS infection) increases your risk as does taking proton pump inhibitors to reduce stomach acid.

http://www.mayoclinic.org/diseases-conditions/c-difficile/symptoms-causes/dxc-20202389
Common symptoms include watery diarrhea 3-4 times a day for 2 or more days and mild abdominal cramping and tenderness

Severe symptoms include watery diarrhea 10-15 times a day, severe abdominal cramping and pain, rapid heart rate, fever, nausea, dehydration, loss of appetite, weight loss, swollen abdomen, kidney failure, and increased white blood cell count.

http://patient.info/health/clostridium-difficile-leaflet
Currently people with C-diff are given an antibiotic such as vancomycin or metronidazole and should have their own room and toilet facilities, making sure to wash hands, toilets, bedpans, bedding, surfaces, and floors often. Caregivers should wear disposable gloves and aprons, washing hands with soap and water before and after attending the infected. Hand gel may not kill the spores.

Unfortunately, there are cases where the standard antibiotics, even Fidaxomicin, a non-absorbed antibiotic with high selectivity to C-diff, also found to inhibit toxin and spore production, didn’t work. There is concern of antibiotic resistance.

http://www.medicalnewstoday.com/releases/224359.php, and http://www.medicalnewstoday.com/articles/251759.php
Somewhat new are fecal transplants, in which feces from a donor are processed in the lab and then injected into the small intestine and right side of the colon. These procedures, performed by only a few doctors nationwide, have proven effective, but some worry about unknown risks.

If you don’t own a jet and aren’t quite ready to introduce someone else’s poop into your body, there’s good news on the horizon.

http://www.nature.com/articles/srep33642
Researchers at Scripps Research Institute in San Diego, CA, have found that salicylanilides, commonly used to deworm sheep, goats, and cattle, stopped the growth of numerous C-diff strains, even some that cause recurrent infections. Closantel, rafoxanide, niclosamide, and oxyclozanide all showed some effectiveness with Closantel and rafoxanide being the best for halting C-diff growth, but also showed some work against “stationary-phase” C-diff cells – the cells responsible for producing the toxins behind inflammation of the colon as well as the spores that persist on surfaces which increase transmission rates.

Also, the low oral bioavailability and high fecal excretion demonstrates an appropriate gut concentration to target C-diff in the colon.

The study authors, after theorizing that the compounds change the electrical properties of the bacterial cell membranes, created new compounds boosting this cell membrane altering effect, which increased the effectiveness. Also, the newly created compounds didn’t affect the beneficial gut bacteria thereby showing C-diff won’t have to evolve to develop resistance.

Researchers are now testing the compounds in animal models and are in the process of trying to license them as a treatment for C-diff in humans.

http://www.wildcondor.com/one-tough-bug.html  For one person’s experience with C-diff while on MSIDS treatment.

Make sure to talk to your health care practitioner about things you can do to lower your risk of C-diff while on MSIDS treatment.

Some suggestions

*Eat a no sugar diet

*Avoid alcohol

*Eat a no to low carbohydrate diet – particularly omitting things such as pasta, bread, rice, potatoes, bananas, and other carbs which have a high glycemic index

*Take copious pre and probiotics to foster a healthy gut micro biome

*Pulse antibiotics rather than using them continuously, or take an antibiotic holiday periodically

*Try and remind yourself that MSIDS treatment is long, so healthy habits are a must to go the distance.  Everything you do early on has long-term ramifications.

Category:

C-diff, Treatment