News

Bakteriophage

1. Phelix Phage Test - New highly specific and sensitive diagnostic method in the sense of direct pathogen detection in the case of borreliosis suspicion

2. Disulfiram - A new substantial therapeutic option in the treatment of tick-borne diseases

Review by Dr. med. Wolfgang Klemann
Internal Medicine Private Practice
Leopoldstr. 17
D-75172 Pforzheim

As of January 2021

1. Phelix Phage Test: A new, very sensitive diagnostic method for the laboratory diagnosis of Lyme disease:

" A breakthrough way to detect intracellular bacteria, and an answer to non-diagnosed ill people"

Excerpts from the test description of the laboratory RED Laboratories NV / SA,

Z 1 Researchpark 100, Zellik 1731, Belgium;

Explanation of why bacteriophages can be used as a diagnostic tool for active bacterial infection (translation by Dr. W. Klemann ) :

" Bacteriop Hagen are among the simplest and most primitive life forms (viruses). They are extremely specific to the bacterial host that they infect (by reprogramming its metabolism) in order to reproduce. They can quickly infect their host and insert their genetic material into their host. As a result, they produce large numbers of copies that can further infect (and in certain cases, decimate) the bacteria causing the infection. They are much more numerous than the bacteria / host cell (there are 10 to 100 bacteriophages per bacterium). "

You can also make the bacteria susceptible to traditional treatment by changing their genetic material. Most importantly, bacteriophages can be lethal (for the host cell). Phages are so small that they can invade bacterial biofilms and destroy them. Such biofilms are an important barrier that bacteria form against antibiotics and they therefore make an important contribution to antibiotic resistance. The ability of the phages to invade biofilms allows them to multiply to a large extent in the localized centers of bacterial infection and to destroy the bacteria contained therein; thereby they (also) achieve a strong but localized therapeutic effect.
Bacteriophages are ubiquitous and part of the natural "ecosystem" of the life and replication cycles of bacteria. The (new) concept is that we are no longer looking for the bacteria, but for their obligatory bacteriophages. The genetic material of the bacteriophage is specific for the bacteria , with which they are associated . This means that different types of bacteria have different bacteriophages. We (RED Laboratories) decided to focus on bacteriophages as targets for the direct detection of infection. Bacteriophages occur only in active bacterial infections ;

A phage-based test is therefore a direct evidence of active infection

Our current phage-based projects also focus on a number of other bacteria known to be involved in chronic bacterial (tick-borne) infections such as Rickettsia, Bartonella, Sutterella and Mycoplasma. Bacteriophages could become a diagnostic tool based on the principle that if (specific) phages are found, live bacteria must also be present. "

Dr. W. Klemann in a case of neuroborreliosis and the initiation of the phage test mentioned above:

30-year-old patient with a cerebrospinal fluid-positive and serologically confirmed neuro-borreliosis with a 3-year medical history. After a tick bite, shoulder and neck pain, headache, swallowing disorders, muscle fasciculations and dysesthesia occurred.
In the phage test there was a positive test result for Borrelia: "Positive Phage Borrelia DNA fragments detected" - this after a 3-month anti-infective combination therapy, whereby there was an improvement, but (unfortunately) no freedom from symptoms. This is a (further) case that proves that there are courses of chronic borreliosis in which a recovery could (unfortunately) not be achieved even after several months of consistent combination antibiosis!

2. Disulfiram - A new substantial therapeutic option in the treatment of tick-borne diseases

“ New aspects for the treatment of Lyme disease - but also co-infections - result from the use of Disulfiram, a drug that was originally used to support alcohol-dependent patients who have managed to become alcohol-abstinent. The effect of disulfiram ( trade names including Antabus, Esperal ) is that even small amounts of alcohol can lead to severe headaches, as an enzyme for the breakdown of alcohol is blocked, but acetaldehyde then accumulates, which is known as headache triggers. Disulfiram is said to use this mechanism to discourage alcohol-dependent patients from drinking alcohol again.

The above-mentioned disulfiram has now proven to be an extremely effective anti-infectant in corresponding recent studies - it appears to be effective against Borrelia, but also against the malaria pathogen (and thus also against Babesia), against staphylococci, streptococci and Bartonella! This emerges from an overview article by our American colleague Daniel Kinderlehrer:

https://www.lymedisease.org/?s=disulfiram+breakthrough

A treatment attempt with disulfiram seems to me justified in such cases, especially since few interactions with other drugs are reported - starting in low doses as stated in the article mentioned - so the tolerability can be assessed well. Disulfiram is initially taken alone, which of course simplifies therapy considerably.

About the mechanism of action of disulfiram:

The effect of disulfiram is probably due to the fact that the long molecule with 4 sulfur atoms in the center is shaped into a ring and thus becomes a chelate (ring-shaped molecule), which contains positively charged particles, i.e. cations such as Fe 2+, Cu 2+ , Manganese 2+, etc. binds. However, all bacteria and unicellular organisms need cations (as co-enzymes) to maintain their normal metabolism - disulfiram is apparently intracellular - this mechanism deprives the bacteria / unicellular organisms of the necessary cations, which ultimately leads to the death of microorganisms. Disulfiram is therefore a new antibiotic with a broad spectrum of activity.

Contraindications to disulfiram

Pronounced psychiatric comorbidities (acute manias, psychoses, suicidality), especially with high impulsiveness on the symptom level;
Liver dysfunction (transaminases, alkaline phosphatase, GGT> 3 times the normal limit value);
Epilepsy;
Peripheral polyneuropathy;
Pregnancy;
Kidney or heart disease;
Relative contraindication: diabetes mellitus.

Before therapy

EKG (optional)
Laboratory: liver values (transaminases, alkaline phosphatase, GGT), creatinine
The patient should abstain from alcohol for three days before taking the drug for the first time.

Laboratory diagnostics

The liver-typical enzymes may not exceed 3 times the norm at the start of treatment. It is recommended to check ALAT and ASAT twice a day in the first three months, then 2-4 times a year.

Side effects

Temporary drowsiness, lack of drive, but also increased, allergic skin reaction, headache, diarrhea, constipation, metallic / garlic-like / sulphurous taste in the mouth.
Peripheral neuropathy, characterized by painful tingling paresthesia in the hands and feet.
Occasional loss of libido / impotence after prolonged use (6-12 months).
Drug-induced hepatitis (very rarely 1: 25,000). If this complication occurs, treatment must be terminated and, due to the high risk of recurrence, represents a contraindication for further attempts at treatment with disulfiram.
Cave: cytochrome P-450 inhibition (interaction with some benzodiazepines).

Interactions

Disulfiram enhances the effect of anticoagulant drugs and that of phenytoin by reducing the metabolism of said drugs.
Disulfiram possibly leads to a demethylation of diazepam and chlordiazepoxide, which leads to an increased sedative effect of the corresponding drugs.
A combination with metronidazole can cause confusion.
Interactions see also “drug interaction checker” from Medscape.

There are new aspects in the use of disulfiram in terms of combining disulfiram with antibiotics: Disulfiram can be combined with most antibiotics - see also "Drug Interaction Checker" from Medscape (Internet).

Not least due to the recommendation / positive experience of American colleagues (including R. Horrowitz, D. Kinderlehrer, K. Liegner), I have had disulfiram in combination with antibiotics and - in the case of Babesia co-infection - in combination with atovaquone / proguanil and Primaquine - used; As expected, there was a Herxheimer-like increase in symptoms, so the dose of antibiotics / anti-malarial drugs should be chosen low - in other words:

Disulfiram seems to significantly increase the effects of antibiotics / anti-malarial drugs in most cases, so the dose of antibiotics / anti-malarial drugs must be reduced, but also the dose of disulfiram!

This helps to minimize the rate of side effects of disulfiram, as well as those of antibiotics / anti-malarial drugs. All of these are very hopeful experiences ......

However, it should be noted that regardless of which anti-infectious agent is used, no elimination of pathogens can be achieved by anti-infectives, but at best the death of pathogens and this at the site of the infectious event - in the case of Lyme disease (at the stage of dissemination ) in the tissue, in the walls of the capillaries, etc. - Killed pathogens must then be eliminated by the cellular immune system - but this is initially an inflammatory process and intensifies the original symptoms (Herxheimer reaction) - this can lead to inflammatory redness, possibly pain, dizziness, Cause headaches, itching, red eyes, etc.

Taking this mechanism of action into account, it becomes clear that even disulfiram in combination with anti-infectives does not lead to a quick recovery - this treatment also takes time; However, a significant reduction in the burden of pathogens is achieved, which can ultimately lead to real recovery.

Experience with long-term patients: By using disulfiram in two to four 8-week treatment cycles - most recently in combination with antibiotics in a low dose - recovery was ultimately achieved.

In appropriate cases, I advise attempting treatment with Disulfiram 500 mg (Esperal tablets = trade name of the French preparation) in an initially low dose of 0-0-1 / 4 tablets, initially only every 2nd to every 3rd day (depending on of expected Herxheimer-like intensification of symptoms). In the further course, a gradual dose increase up to a maximum of 0-0-1 / 2 tablets (250 mg / day) recommended over an initial period of 8 weeks, then a disulfiram break of several weeks. Thereafter, possibly a new prescription of disulfiram for 4-8 weeks, again in an initially low dose, depending on the remaining symptoms.

A treatment and dosage example for Lyme disease / Bartonella co-infection:

Start with Esperal 500 mg 0-0-1 / 4, check the liver values after one week !!!!! If the liver-typical enzymes do not increase, add azithromycin 250 mg initially 1-0-0 (azithromycin is effective against Borrelia as well as Babesia and Bartonella!), Provided there is no strong Herxheimer-like increase in symptoms, then additional administration of pyrazinamide 500 mg 0-0-1 - a higher dose is unlikely to be required in the further course as the combination increases the effects of pyrazinamide. Depending on the symptoms, it would then be necessary to decide whether to use further anti-infectives.